Search results for "Phosphor"

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress

2016

Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, …

Effects of Pimozide Derivatives on pSTAT5 in K562 Cells

2017

STAT5 is a transcription factor, a member of the STAT family of signaling proteins. STAT5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), in which this protein is found constitutively activated as a consequence of BCR-ABL expression. The neuroleptic drug pimozide was recently reported to act as an inhibitor of STAT5 phosphorylation and is capable of inducing apoptosis in CML cells in vitro. Our research group has synthesized simple derivatives of pimozide with cytotoxic activity and that are able to decrease the levels of phosphorylated STAT5. In this work we continued the search for novel STAT5 inhibitors, synthesizing compounds in which the benzoimidazol…

2018

Chardonnay wines from Burgundy, obtained from musts with three levels of clarification (Low, Medium and High) during two consecutive vintages (2009 and 2010) and for two kinds of closures (screw caps and synthetic coextruded closures) were analyzed chemically and sensorially. Three bottles per turbidity level were opened in 2015 in order to assess the intensity of the reductive and/or oxidative aromas (REDOX sensory scores) by a trained sensory panel. The chemical analyses consisted in polyphenols and colloids quantification, followed by a proteomic characterization. For the two vintages, the REDOX sensory scores appeared to be driven both by the type of closure and to a lesser extent by th…

Hsp60 Post-translational Modifications: Functional and Pathological Consequences.

2020

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…

Impact of Oxidative Stress on the Heart and Vasculature

2017

Abstract Vascular disease and heart failure impart an enormous burden in terms of global morbidity and mortality. Although there are many different causes of cardiac and vascular disease, most causes share an important pathological mechanism: oxidative stress. In the failing heart, oxidative stress occurs in the myocardium and correlates with left ventricular dysfunction. Reactive oxygen species (ROS) negatively affect myocardial calcium handling, cause arrhythmia, and contribute to cardiac remodeling by inducing hypertrophic signaling, apoptosis, and necrosis. Similarly, oxidative balance in the vasculature is tightly regulated by a wealth of pro- and antioxidant systems that orchestrate r…

Evaluation of Carotenoids Protection Against Oxidative Stress in the Animal Model Caenorhabditis elegans

2019

The nematode Caenorhabditis elegans is a versatile and powerful model organism for animal experimental research and, despite being an invertebrate, displays remarkably similar molecular bases and conserved cellular pathways to those of humans. Oxidative stress is an etiological factor that influences numerous diseases, degenerative processes and aging. C. elegans has revealed as an opportune and feasible organism to investigate the antioxidant effects of different bioactives or complex food matrices, and a number of protocols have been developed by using different oxidative stressors. Carotenoids are recognized as quenchers and scavengers of reactive oxygen species, and many of their relate…

The application of casein phosphopeptide and amorphous calcium phosphate with fluoride (CPP-ACPF) for restoring mineral loss after dental bleaching w…

2018

Abstract Objective To conduct an in vitro evaluation of the effect of casein-phosphopeptide and amorphous calcium phosphate with fluoride [CPP-ACPF] upon the calcium [Ca] and phosphorus [P] composition and morphology of dental enamel and dentin after the application of two bleaching agents: 37.5% hydrogen peroxide [HP]) and 35% carbamide peroxide [CP]. Materials and methods The crowns of 40 extracted human teeth were divided into four groups (n = 10 each). The crowns were sectioned along the cervical-incisal axis, and each half was embedded in acrylic resin, leaving a window 3 mm in diameter to explore the enamel or dentin (according to the study group involved). Groups 1a and 1b correspond…

An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro

2017

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anticancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effect…

Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model

2018

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…

Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far

2018

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare metabolic autosomal recessive disease, caused by mutations in the nuclear gene TYMP which encodes the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of the deoxyribonucleosides thymidine and deoxyuridine, and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. Clinically, MNGIE is characterized by gastrointestinal and neurological manifestations, including cachexia, gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, ophthalmoplegia and ptosis. The disease is …