Expression of heat shock proteins in bladder cancers

Evalutaion of HSP60, Procaspase-3 and P53 expression after oxydative stress in NCI-H292 cells.

Human recombinant vasostatin-1 may interfere with cell-extracellular matrix interaction

Effects of P53 and HSP70 expression in a model of oxidative-stress induced apoptosis in tumoral cells

Chaperonology: A novel research field for experimental medicine in the XXI century.

Extracellular Vesicle-Mediated Cell–Cell Communication in the Nervous System: Focus on Neurological Diseases

Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear…

Expression of Heat Shock Protein in bladder cancers.

Expression of Heat Shock Protein in bladder cancers.

Brain Tumor-Derived Extracellular Vesicles as Carriers of Disease Markers: Molecular Chaperones and MicroRNAs

Primary and metastatic brain tumors are usually serious conditions with poor prognosis, which reveal the urgent need of developing rapid diagnostic tools and efficacious treatments. To achieve these objectives, progress must be made in the understanding of brain tumor biology, for example, how they resist natural defenses and therapeutic intervention. One resistance mechanism involves extracellular vesicles that are released by tumors to meet target cells nearby or distant via circulation and reprogram them by introducing their cargo. This consists of different molecules among which are microRNAs (miRNAs) and molecular chaperones, the focus of this article. miRNAs modify target cells in the…

Extracellular release of HSP60 from tumor cells occurs via various secretory pathways

Hsp60 is actively secreted by human tumor cells

Background Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings S…

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

This review will analyze growing evidence suggesting a convergence between two major areas of research: Alzheimer’s disease (AD) and chaperonopathies. While AD is a widely recognized medical, public health, and social problem, the chaperonopathies have not yet been acknowledged as a related burden of similar magnitude. However, recent evidence collectively indicates that such possibility exists in that AD, or at least some forms of it, may indeed be a chaperonopathy. The importance of considering this possibility cannot be overemphasized since it provides a novel point of view to examine AD and potentially suggests new therapeutic avenues. In this review, we focus on the mitochondrial chape…

Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of t…

Evaluation of hsp60, procaspase-3 and p53 expression after oxydative stress in H292 cells

Clinical anatomic, immunomorphologic and molecular anatomic data suggest interplay of thyroidal molecules, autoantibodies and Hsp60 in Hashimoto’s disease

Hsp60 is, typically, a mitochondrial protein, but it also occurs in the cytosol, vesicles, and plasma membrane, and in the intercellular space and biological fluids, e.g., blood. Changes in the levels and distribution of Hsp60 are linked to several pathologies, including cancer and chronic inflammatory and autoimmune disorders. What is the histopathological pattern of Hsp60 in the thyroid of Hashimoto’s patients? Are there indications of a pathogenic role of Hsp60 that may make Hashimoto’s thyroiditis a chaperonopathy? Experiments reported here provide information regarding those questions. We found by various immunomorphological techniques increased levels of Hsp60 in the thyroid from HT p…

Oxidative stress apoptosis in carcinogenesis: molecular players and interactions.

Cisplatin-induced endoreduplication in CHO cells: DNA damage and inhibition of topoisomerase II.

It has been proposed that polyploid cells that arise during a variety of pathological conditions and as a result of exposure to genotoxicants, typically in the liver, become aneuploid through genetic instability. Aneuploidy contributes to, or even drives, tumour development. We have assessed the capacity of the drug cisplatin, one of the most commonly used compounds for the treatment of malignancies, to induce endoreduplication, a particular type of polyploidy, in cultured Chinese hamster AA8 cells. Taking into account that any interference with DNA topoisomerase II (topo II) function leads to endoreduplication, we have found that treatment of the cells with this platinum compound results i…

HSP60 and HASP10 overexpression in metastatic colon cancer

Extracellular heat shock proteins in cancer: From early diagnosis to new therapeutic approach

In cancer, human cells lose the ability to properly control the series of events that occur constantly during cell growth and division, including protein expression, stability, and dynamics. Heat shock proteins (Hsps) are key molecules in these events, constitutively expressed at high levels and could furthermore be induced by the response to cancer-induced stress. In tumor cells, Hsps have been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis; in some cases, they can be overexpressed and dysregulated, representing important cancer hallmarks. In the past few years, it has been demonstrated that Hsps can be released by tumor cells through s…

Serological, immunomorphological and bioinformatics analyses suggest Hsp60 is involved in Hashimoto’s thyroiditis pathogenesis.

EXTRACELLULAR RELEASE OF HSP60 FROM TUMOR CELLS

A multipronged approach to unveil the emerging role of Hsp60 in chronic obstructive pulmonary disease

Inflammation is a major component of chronic obstructive pulmonary disease (COPD) and its cause and mechanisms are still incompletely understood. For example, the role of heat shock proteins (Hsps), many of which are molecular chaperones, has not been explored in detail in COPD, despite the fact that these molecules are known to participate in inflammation in other diseases. It has been shown that extracellular Hsps can signal certain types of T cells, macrophages, dendritic cells, and neutrophils and, thereby, elicit inflammation and immunity. However, these phenomena have not been investigated in COPD despite: a) the increasing awareness of Hsp participation in inflammation and immunity; …

Study of the effects of Pleurotuseryngii var. eryngii on heat shock proteins and cytokines levels in a mouse model of colon carcinoma

Medicinal mushrooms are wonderful source of nutraceuticals with a wide range of benefit for human health. The current anti-cancer therapy is not always target specific and often is associated with complications for patients. Therefore new effective and less toxic therapeutic approaches are needed. Heat shock proteins (Hsps) are highly expressed in a variety of cancer types contributing to tumor cell propagation. Here, we treated C26 colon cancer cells with a cold-water extracts of an edible mushrooms Pleurotuseryngii var. eryngii (Pleuery). Hsp90, 70, 60 and 27 levels were measured by western blotting and immunofluorescence analysis. Moreover, we evaluated Pleueryanti cancer effect in an an…

Molecular profile study of extracellular vesicles for the identification of useful small “hit” in cancer diagnosis

Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognosis, monito…

The Odyssey of Hsp60 from Tumor Cells to Other Destinations Includes Plasma Membrane-Associated Stages and Golgi and Exosomal Protein-Trafficking Modalities

BACKGROUND: In a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here. PRINCIPAL FINDINGS: We found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevent…

Evaluation od hsp60, pro-caspase-3 and p53 expression after oxidative stress in NCI-H292 cells

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Expos…

Hsp60 secretion and migration from cancer cells: a proposal for a multistage pathway

Exosome levels in human body fluids: A tumor marker by themselves?

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discrimin…

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in NCI-H292 cancer cells

Abstract Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole) 2 (H 2 O) 2 ](ClO 4 ) 2 , CubipyOXA , a copper-containing compound with cytotoxic properties. We treated cells with various doses of the compound and measured cell viability; apoptosis indicators; and le…

Immunophenotypical characterization of a case of pulmonary metastatic biphasic synovial sarcoma: anatomoclinical aspects and short review of literature

Exosome Involvment in Hsp60 secretion by tumor cells.

A comparative analysis of the products of GROEL-1 gene fromChlamydia trachomatisserovar D and the HSP60 var1 transcript fromHomo sapienssuggests a possible autoimmune response

Summary Chlamydia trachomatis serovar D produces large quantities of HSP60-1 during infections, which accumulate inside the host cell inducing autoimmunity. We compare the aminoacid sequences of the human HSP60 with the bacterial counterpart to better elucidate how CTHSP60 may simulate HSP60 from human origin during infection and may induce an autoimmune response. As a result of the comparison we suggest several possible epitopes of the CTHSP60, which may induce autoimmunity.

Composti curcumin-like come agenti neuro-protettori. Interazione con HSP60

La Malattia di Alzheimer rappresenta una sfida fondamentale del XXI secolo per la salute pubblica. Le terapie attualmente utilizzate per la cura dell’Alzheimer si basano sugli aspetti sintomatici della patologia [1]. Un importante ruolo nella malattia è rivestito dalle Heat shock proteins (HSPs), proteine che presiedono al controllo del ripiegamento proteico [2]. Recentemente, è stato dimostrato che HSP60 media la traslocazione del Precursore della Proteina Amiloide (APP) e del Peptide Beta Amiloide (Aβ) nei mitocondri, portando alla perdita della funzionalità dell’organulo [3]. Nel campo degli approcci delle terapie potenziali, la curcumina sta emergendo come lead compound per lo sviluppo …

Exosomal Hsp60 in human colon cancer

Comparative analysis of Hsp10 and Hsp90 in large bowel healthy mucosa and adenocarcinomas

Heat shock proteins (Hsps) are an important class of molecules with various functions. Their classic role is to assist other proteins in folding and re-folding and, when proteins are defective or irreversibly misfolded, to drive their degradation. For this reason, some Hsps are also named molecular chaperones. During evolution, this class of proteins has also acquired extrachaperoning roles such as participation in immune system regulation, cell differentiation, programmed cell death and carcinogenesis. Hsp10 is a partner of Hsp60 in the Hsp60/10 folding machine, but numerous scientific studies have shown that Hsp10 may also play other roles. In fact, Hsp10 seems to have an immunomodulatory…

Expression of CD1a by Barrett’s metaplasia epithelial cells

RESEARCH OF UNDIFFERENTIATED CELLS IN ADULT RAT MYOCARDIUM

CD1a expression in Barrett’s oesophagus: new role for an old molecule against metaplastic progression

Multi-chaperone – interactors network (mtcin) in mitochondria: role in neoplasm development and methodology of analysis.

Distinctive patterns of Hsp60 levels and localization in human colon mucosa.

Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 w…

Hsp60 and Hsp10 overexpression in metastatic colon cancer.

Molecular chaperones expression levels and localization in non-tumoral and tumoral thyroid tissues

Papillary thyroid carcinoma (PTC) is the most frequently occurring subtype of thyroid cancer. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normality and pathology. Recent data indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment(1). Heat Shock Protein (HSPs) are often overexpressed during carcinogenesis and different studies shown that they can be released by tumors cells and that the mechanism of release is mediated by EXs pathway. In this project we performed an immunomorphological study to investigate Hsp60, 90,70,27 levels expression profile…

Air Pollution: Role of Extracellular Vesicles-Derived Non-Coding RNAs in Environmental Stress Response

Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRN…

A novel copper compound, CuNV110, induces apoptosis in tumor cells by dissociation of the Hsp60- pro-caspase 3 complex

The biological activity of CuNV1110, a novel copper chemical compound, has been recently studied on cancer cells and it has been showed that it reduces the cell viability, in a dose and time dependent manner, and induces cell apoptosis. In this study we evaluated the possible mechanisms by which CuNV1110 induces cell apoptosis. In particular we looked at its effects on Hsp60 levels and caspase 3 activation. We used an in vitro model of a pulmonary mucoepidermoid carcinoma (NCI-H292 cells). We found that CuNV1110 reduces the cell viability and induces cell apoptosis in a dose/time dependent manner. Then, we found that Hsp60 levels decrease with the increasing concentrations of CuNV110; by co…

The pathogenetic role of the chaperonin Hsp60 in chronic obstructive pulmonary disease: new data and perspectives

Trafficking and secretion patterns of Hsp60 in tumor cells.

CuNV1110 induces dissociation of the Hsp60-pro-caspase 3 complex and activation of apoptosis in tumor cells

EVALUATION OF HSP60, PROCASPASE-3 AND p53 EXPRESSION AFTER OXYDATIVE STRESS IN NCI-H292 CELLS

Post-translational modifications of hsp60 and its extracellular release via exosomes are induced by the histone deacetylase inhibitor (HDACi) SAHA in the mucoepidermoid tumor H292 cells.

The chaperonin Hsp60 has multiple functions, among which that of supporting the growth of some type of tumours (1). HDACi (histone-deacetylase inhibitors) are drugs that regulate gene expression via modulation of epigenetic mechanisms, and induce tumor-cell death (2). Here, we show that in the tumor cells H292 the HDACi SAHA decreases the intracellular level of Hps60 and promotes its extracellular trafficking by exosomal vesicles. SAHA caused a time- and dose-dependent decrease in cell viability with a G/2M cell-cycle arrest at 24 h and cell death at 48 h. These effects were accompanied by production of reactive oxygen species and mitochondrial membrane-potential dissipation. The marked dec…

The triad hsp60-mirnas-extracellular vesicles in brain tumors: Assessing its components for understanding tumorigenesis and monitoring patients

Brain tumors have a poor prognosis and progress must be made for developing efficacious treatments, but for this to occur their biology and interaction with the host must be elucidated beyond current knowledge. What has been learned from other tumors may be applied to study brain tumors, for example, the role of Hsp60, miRNAs, and extracellular vesicles (EVs) in the mechanisms of cell proliferation and dissemination, and resistance to immune attack and anticancer drugs. It has been established that Hsp60 increases in cancer cells, in which it occurs not only in the mitochondria but also in the cytosol and plasma-cell membrane and it is released in EVs into the extracellular space and in cir…

Inhibition of Hsp60 expression by doxorubicin and replicative senescence instauration in mucoepidermoid carcinoma cells

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms.Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed.The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pa…

Effetti della temperatura dell'acqua sull'idratazione di nuotatori di fondo

The effects of oxidative stress on neoplastic cell survival.

EXOSOMES: CAN DOCTORS STILL IGNORE THEIR EXISTENCE?

With this invited commentary we want to draw the attention of young medical doctors, the main readers of this journal, towards the existence and importance of a group of nanovesicles released by human cells: the exosomes. These vesicles are incontinently se-creted as a mean of cell-to-cell communication. They are involved in a number of physiol-ogic processes as well as in the pathogenesis of, virtually, all human diseases. They can be isolated from all biological fluids, like blood, urine, sweat, sperm, crevicular fluid, bile, etc., and their composition in terms of proteins, RNA and lipids is different in pathology that in physiologic conditions. It is therefore possible to predict that t…

Human Hsp60 with Its Mitochondrial Import Signal Occurs in Solution as Heptamers and Tetradecamers Remarkably Stable over a Wide Range of Concentrations

It has been established that Hsp60 can accumulate in the cytosol in various pathological conditions, including cancer and chronic inflammatory diseases. Part or all of the cytosolic Hsp60 could be naive, namely, bear the mitochondrial import signal (MIS), but neither the structure nor the in solution oligomeric organization of this cytosolic molecule has still been elucidated. Here we present a detailed study of the structure and self-organization of naive cytosolic Hsp60 in solution. Results were obtained by different biophysical methods (light and X ray scattering, single molecule spectroscopy and hydrodynamics) that all together allowed us to assay a wide range of concentrations of Hsp60…

Ethanol-Mediated Stress Promotes Autophagic Survival and Aggressiveness of Colon Cancer Cells via Activation of Nrf2/HO-1 Pathway

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetyl…

CD1A expression in Barrett’s oesophagus: new role for an old molecule against the metaplastic progression

Hsp60, a Novel Target for Antitumor Therapy: Structure-Function Features and Prospective Drugs Design

Heat shock protein 60 kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60's function, especially in prokaryotes, fundamental issues still remain unexplored, including the definition of its role in cancer. Key questions still unanswered pertain to the differences in structure-function features that might exist between the well-studied prokaryotic GroEL and the largely unexplored eukaryotic Hsp60 proteins. In this article we discuss these …

CD1A expression in Barrett's oesophagus: new role for an old molecule against metaplastic progression

On the Choice of the Extracellular Vesicles for Therapeutic Purposes

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of diseas…

Expression of CD1a by Barrett’s metaplasia epithelial cells.

Hsp60 from cancer cells can reach near and distant targets: A proposal for a multistage pathway

Cancer cells have means to influence other cells in their vicinity and distant, and in this signal-delivering mechanisms the chaperonin Hsp60 plays a role, which is currently being recognized as potentially crucial for the growth and dissemination of at least certain types of tumors. In order to arrive at its destination, Hsp60, a typical resident of mitochondria in normal and tumor cells, leaves the organelle and reaches the blood. In the latter, Hsp60 can travel and arrive at targets situated far away from its origin. The details of the route followed by Hsp60 and their molecular mechanisms have not yet been fully elucidated. We investigated Hsp60 levels and secretion in normal and tumor …

European Week of Sport: innovative initiative of European Commission that inspires children to be active

BAC KGROU ND: Estimates indicate that more than one third of European adults are inactive, despite the known benefits of physical activity. In 2015 the European Commission launched the European Week of Sport (EWoS), to encourage people to engage in sport and physical activity. The aim of this study was to evaluate if participation in the EWoS could motivate children to participate in physical activity in future. METHOD S: A total of 10,892 children (aged 6-14), from 6 EU cities (Palermo, Italy; Ankara, Turkey; Lousada, Portugal; Gardabaer, Iceland; Rijeka, Croatia; Albacete, Spain), were enrolled in sport activities (running sport event, extra hours of physical activity, seminars on physica…

Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

Among diseases whose cure is still far from being discovered, Alzheimer’s disease (AD) has been recognized as a crucial medical and social problem. A major issue in AD research is represented by the complexity of involved biochemical pathways, including the nature of protein misfolding, which results in the production of toxic species. Considering the involvement of (mis)folding processes in AD aetiology, targeting molecular chaperones represents a promising therapeutic perspective. This review analyses the connection between AD and molecular chaperones, with particular attention toward the most important heat shock proteins (HSPs) as representative components of the human chaperome: Hsp60,…

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. METHODS: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and sp…

DNA sequence and comparative analysis of homologous HSP60 genes of Chlamydia trachomatis serovar D and Homo Sapiens

Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery

BACKGROUND: Heat shock protein 60 (Hsp60) is a chaperonin involved in tumorigenesis, but its participation in tumor development and progression is not well understood and its value as a tumor biomarker has not been fully elucidated. In the current study, the authors presented evidence supporting the theory that Hsp60 has potential as a biomarker as well as a therapeutic target in patients with large bowel cancer. METHODS: The authors studied a population of 97 subjects, including patients and controls. Immunomorphology, Western blot analysis, and quantitative real-time polymerase chain reaction were performed on tissue specimens. Exosomes were isolated from blood and characterized by electr…

Curcumin-Like Compounds as Neuroprotective Agents: Interactions with HSP60 and Amyloid Beta Peptide

Alzheimer’s Disease (AD) represents a fundamental challenge for public health in the 21st century. Current AD therapies largely focus on symptomatic aspects of the clinical pathology, but they have yet to demonstrate any major impact on the disease progression [1]. The most important role of the research aimed at fighting the AD is the development of neuro-protective agents, able to interfere with the protein aggregation process whose clinical signature is represented by the plaques deposition. An important role in AD’s framework could be played by Heat shock proteins (HSPs), highly regulated proteins that mediate the proteins proper folding and promote recovery of their native conformation…

Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia.

Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an Hsp60-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is di…

Exosomal HSP60 levels and related miRNAs in brain tumors

In cancer, Extracellular Vesicles (EVs), such as exosomes, contribute to tumor progression by regulating local and systemic parameters. Since exosomes are released into body fluids, they may be used in nanomedicine as a valuable source of diagnostic biomarkers. The prognosis of brain tumors is poor even after surgical resection followed by post-operatory chemo- and radio-therapies and it is cogent to find innovative treatments. The discovery that molecular chaperones can be determinant factors in tumorigenesis and the increasing understanding of exosomes, particularly in what refers to their release by tumor cells and contents, including chaperones and miRNA, provide elements to develop nov…

HSP60 and HSP10 overexpression in metastastic colon cancer

The histone deacetylase inhibitor SAHA induces HSP60 nitration and its extracellular release by exosomal vesicles in human lung-derived carcinoma cells

// Claudia Campanella 1, 2, * , Antonella D'Anneo 3, * , Antonella Marino Gammazza 1, 2, * , Celeste Caruso Bavisotto 1, 2 , Rosario Barone 1, 2 , Sonia Emanuele 4 , Filippa Lo Cascio 1 , Emanuele Mocciaro 1 , Stefano Fais 5 , Everly Conway De Macario 6 , Alberto J.L. Macario 2, 6 , Francesco Cappello 1, 2 , Marianna Lauricella 4 1 Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy “Emerico Luna”, University of Palermo, Palermo, Italy 2 Euro-Mediterranean Institute of Science and Technology, Palermo, Italy 3 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, Palermo, Ita…

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence.

Hsp60 is a pro-carcinogenic chaperonin in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not known whether or not doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of this protein. We used the human lung mucoepidermoid cell line NCI-H292 and different doses of doxorubicin to measure cell viability, cell cycle progression, cell senescence indicators, Hsp60 levels and its post-translational modifications as well as the release of the chaperonin into the extracellular environment. Cell viability was reduced in relation to doxorubicin dose and this was paralleled by the appearance of cell senescence markers. Con…

Effects of Chitosan on Plasma Lipids and Lipoproteins

Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and triglycerides by 19%, with a concomitant 14% increase in high-…

The molecular anatomy of human Hsp60 and its effects on Amyloid-β peptide

Heat Shock Protein 60 (HSP60) is ubiquitous and highly conserved, being present in eukaryotes and prokaryotes, including pathogens. This chaperonin is typically considered a mitochondrial protein but it is also found in other intracellular sites, extracellularly and in circulation. HSP60 is an indispensable component of the Chaperoning System and plays a key role in protein quality control, preventing off-pathway folding events and refolding misfolded proteins. This makes HSP60 a putative therapeutic agent for neurodegenerative diseases associated with aggregation of misfolded proteins, for example, Alzheimer’s Disease. We produced and purified recombinant human HSP60 and investigated the e…

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells.

The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial−mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of…

Circulating exosomal Hsp60 as a new marker of colon cancer.

Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin

Luteolin and quercetin are widely distributed plant flavonoids that possess a variety of chemical and biological activities, including free-radical scavenging and antioxidant activity. Recently, both flavonoids have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells. Because interference with the function of topo II to resolve DNA entanglement at the end of re…

Human HSP10 variants downregulation after cigarette smoke extract exposure in lung cells

The impact of cigarette-smoke stress (a form of oxidative stress) on human lung fibroblasts and epithelial cells, particularly its effect on Hsp10 expression, has not been characterized despite the fact that a role for mitochondrial chaperonins in the development of lung diseases, ranging from chronic obstructive pulmonary disease to bronchial carcinogenesis, has been suggested (1). We studied the effects of non-lethal doses of cigarette smoke extract (CSE) on the expression of Hsp10 in human lung fibroblasts (HFL-1 line) and epithelial cells (16HBE line). Proteomics was carried out using 2D-IPG, silver stain, western blotting, and mass-spectrometry; mRNA was measured by RT-PCR. Database se…

EFFECTS OF CONJUGATED LINOLEIC ACID AND RESISTANCE TRAINING IN RECREATIONAL ATHLETES

Conjugated linoleic acid (CLA) is a mixture of positional and geometrical isomers of linoleic acid, that are known to posses several physiological effects such as enhancing immune response, reducing arteriosclerosis risk, and inhibiting carcinogenesis. Over the last decade, the use of CLA supplement has become widespread among elite and recreational athletes because it should increase training effects, improve fat oxidation, increase energy delivery, reduce body weight, improve lipid profile, and so on. The purpose of this project is to investigate whether CLA supplementation after a resistance training session affects general markers of muscle damage, total testosterone, cortisol and sex h…

Chaperonology: The Third Eye on Brain Gliomas

The European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial has validated as a current regimen for high-grade gliomas (HGG) a maximal safe surgical resection followed by radiotherapy with concurrent temozolamide. However, it is essential to balance maximal tumor resection with preservation of the patient&rsquo

Chaperonin of Group I: Oligomeric spectrum and biochemical and biological implications

Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still inc…

Endoreduplication induced in cultured Chinese hamster cells by different anti-topoisomerase II chemicals

With the ultimate purpose of testing the hypothesis that, as shown in yeast mutants, any malfunction of DNA topoisomerase II might result in aberrant mitosis due to defective chromosome segregation, we have chosen three chemicals of different nature, recently reported to catalytically inhibit the enzyme. The endpoint selected to assess any negative effect on the ability of topoisomerase II to properly carry out decatenation of fully replicated chromosomes in the G2/M phase of the cell cycle was the presence of metaphases showing diplochromosomes as a result of endoreduplication, i.e. two successive rounds of DNA replication without intervening mitosis. The anti-topoisomerase drugs selected …

JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii without affecting tumor growth or cachexia.

In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The eff…

HSP60 and HSP10 overespression in metastatic colon cancer

Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-cell Communication

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exoso…

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is…

Human primary macrophages scavenge AuNPs and eliminate it through exosomes. A natural shuttling for nanomaterials.

Abstract The use of nanomaterials is increasing but the real risk associated with their use in humans has to be defined. In fact, nanomaterials tend to accumulate in organs over a long period of time and are slowly degraded or eliminated by the body. Exosomes are nanovesicles actively shuttle molecules, including chemical products and metals, through the body. Macrophages scavenge the body from both organic and inorganic substances, and they use to release high amounts of exosomes. We hypothesized that macrophages may have a role in eliminating nanomaterials through their exosomes. We treated human primary macrophages with 20 nm gold nanoparticles (AuNPs), analyzing the presence of AuNPs in…

Exosomal Hsp60: A Tumor Biomarker?

Exosomes (EXs) are extracellular vesicles containing proteins, DNA, mRNA, non-coding RNAs, such as miRNAs, and lipid. The EXs can be easily isolated from different biological fluids and their content is considered a potential biomarker in various diseases, such as cancer. EXs play an important role in intercellular communication, permitting cells to exchange proteins, lipids, and genetic material in normal and pathological conditions. New data have shown that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. Heat shock proteins 60 kDa (Hsp60) is classically considered mitochondrial proteins with different biological roles. In recent y…

Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics

Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis. Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization. This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HS…

Hsp10: Anatomic distribution, functions, and involvement in human disease

There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and sec…

Naïve Hsp60, similarly to GroEL, oligomerizes to build heptameric and tetradecameric structures.

Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surg…

Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment.

Introduction: Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer. Many studies have fo…

Heat shock proteins may have effects on cellular senescence and may lead to neoplastic transformation

The high rate of endoreduplication in the repair deficient CHO mutant EM9 parallels a reduced level of methylated deoxycytidine in DNA

It has been recently proposed that hypomethylation of DNA induced by 5-azacytidine (5-azaC) leads to reduced chromatid decatenation that ends up in endoreduplication, most likely due to a failure in topo II function [S. Mateos, I. Domínguez, N. Pastor, G. Cantero, F. Cortés, The DNA demethylating 5-azaC induces endoreduplication in cultured Chinese hamster cells, Mutat. Res. 578 (2005) 33-42]. The Chinese hamster mutant cell line EM9 has a high spontaneous frequency of endoreduplication as compared to its parental line AA8. In order to see if this is related to the degree of DNA methylation, we have investigated the basal levels of both endpoints in AA8 and EM9, as well as the effect of ext…

HSP60 is a ubiquitous player in the physiological and pathogenic interactions between the chaperoning and the immune systems

HSP60 participates in many interactions between the system integrated by all chaperones and closely associated molecules (chaperoning system or CS) and the immune system (IS). These interactions occur constantly to maintain normal cell physiology but, occasionally, they are perturbed and become mediators of pathologic events that may lead to disease. This switch to pathology may be initiated by various factors, genetic or acquired, which cause qualitative and/or quantitative modifications of HSP60, or immune crossreactivity between the human and microbial chaperonin orthologs, or a break in the balance between the pro- and anti-inflammatory actions of the chaperonin. Thus, autoimmune and ch…

Hsp60 Post-translational Modifications: Functional and Pathological Consequences.

Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The questio…

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of …

INDUCIBLE NITRIC OXIDE SINTHASE (iNOS) PROTECTS THE HUMAN BRONCHIAL EPHITELIUM EXPOSED TO OXIDANTS BY APOPTOSIS

Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their…

Functions and Therapeutic Potential of Extracellular Hsp60, Hsp70, and Hsp90 in Neuroinflammatory Disorders

Neuroinflammation is implicated in central nervous system (CNS) diseases, but the molecular mechanisms involved are poorly understood. Progress may be accelerated by developing a comprehensive view of the pathogenesis of CNS disorders, including the immune and the chaperone systems (IS and CS). The latter consists of the molecular chaperones; cochaperones; and chaperone cofactors, interactors, and receptors of an organism and its main collaborators in maintaining protein homeostasis (canonical function) are the ubiquitin–proteasome system and chaperone-mediated autophagy. The CS has also noncanonical functions, for instance, modulation of the IS with induction of proinflammatory cytokines. …

Exosomal Hsp60 levels and related miRNA in brain tumor cells

One of the many pathologic conditions still without a satisfactory solution is that of brain tumors. The prognosis is poor even after surgical resection followed by post-operatory chemo- and radio-therapie (1). It is, therefore, cogent to find innovative treatment tools. Three recent developments may provide elements to discover novel treatment strategies and means. These developments are: the discovery that molecular chaperones can be determinant factors in the process of tumorigenesis (2); the elucidation of the role of miRNAs in gene regulation and determination of protein functions, including molecular chaperones; in the various cell compartments (3);the increasing understanding and cha…

Silybin enhances mitochondrial function and inhibits NFkB activation in murine nonalcoholic fatty liver disease

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Inducible nitric oxide synthase (iNOS) protects the human bronchial epithelium exposed to oxidants by apoptosis

Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.

This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…

Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?

To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data sug…

Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 α1 expression

AbstractHeat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activa…

Effects of Pleurotus eryngii var. eryngii in "in vitro" and "in vivo" cancerogenetic models

Heat shock proteins (Hsps) are highly expressed in a variety of cancer types contributing to tumor cell propagation and protection against apoptosis [1]. The current anti-cancer therapy is not always target specific and often is associated with complications for patients, Therefore new effective, specific and less toxic therapeutic approaches are needed. Medicinal mushrooms have emerged as wonderful source of nutraceuticals, anti-oxidants, anticancer, prebiotic, anti-inflammatory, cardiovascular, anti-microbial, and anti-diabetic. The ongoing research projects are aimed to promote mushrooms as new generation ‘‘biotherapeutics’’[2]. The aim of this study was to evaluate whether the cold-wate…

Hsp60/procaspase 3 complex formation in human cells: impact on apoptosis and carcinogenesis.

Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.

BackgroundIt is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.Methods and resultsBronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between th…

Heat shock protein 60 (Hsp60) modulation by the Histon Deacetylase Inhibitor (HDAC-i) SAHA in mucoepidermoid tumor H292 cells

Chaperonology: a novel research field for experimental medicine in XXI century.

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis.

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on …

NUTRITION IN IBD PATIENT'S: WHAT ARE THE PROSPECTS?

Summary: Inflammatory Bowel Disease (IBD) is a chronic disorder characterized by a relapsing-remitting course, which alternates between active and quiescent states, ultimately impairing a patients quality of life. The two main types of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). In physiological conditions the gut is costantly exposed to various antigens, commensal microflora and pathogens and the inflammatory response is finely balanced. It is thought that a vast number of environmental risk factors may be implicated in the development of IBD, including smoking factors, dietary factors, psycological stress, use of non-steroidal anti-inflammatory drugs and oral contraceptives,…

The DNA topoisomerase II catalytic inhibitor merbarone is genotoxic and induces endoreduplication

Abstract In the last years a number of reports have shown that the so-called topoisomerase II (topo II) catalytic inhibitors are able to induce DNA and chromosome damage, an unexpected result taking into account that they do not stabilize topo II-DNA cleavable complexes, a feature of topo II poisons such as etoposide and amsacrine. Merbarone inhibits the catalytic activity of topo II by blocking DNA cleavage by the enzyme. While it was first reported that merbarone does not induce genotoxic effects in mammalian cells, this has been challenged by reports showing that the topo II inhibitor induces efficiently chromosome and DNA damage, and the question as to a possible behavior as a topo II p…

Studying embryonic lung development by tissue engineering: a novel three-dimensional model