Search results for " histones"
showing 10 items of 14 documents
Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells.
2018
Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of cellular responses triggered by histones is capital to design effective therapeutic strategies. Here we report how extracellular histones induce autophagy and apoptosis in a dose-dependent manner in cu…
Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
2017
Abstract Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone‐mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose‐dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase‐2 (COX‐2) and prostac…
H1.0 Linker Histone as an Epigenetic Regulator of Cell Proliferation and Differentiation
2018
H1 linker histones are a class of DNA-binding proteins involved in the formation of supra-nucleosomal chromatin higher order structures. Eleven non-allelic subtypes of H1 are known in mammals, seven of which are expressed in somatic cells, while four are germ cell-specific. Besides having a general structural role, H1 histones also have additional epigenetic functions related to DNA replication and repair, genome stability, and gene-specific expression regulation. Synthesis of the H1 subtypes is differentially regulated both in development and adult cells, thus suggesting that each protein has a more or less specific function. The somatic variant H1.0 is a linker histone that was recognized…
Physical exercise as an epigenetic modulator: Eustress, the "positive stress" as an effector of gene expression.
2012
Physical exercise positively influences epigenetic mechanisms and improves health. Several issues remain unclear concerning the links between physical exercise and epigenetics. There is growing concern about the negative influence of excessive and persistent physical exercise on health. How an individual physically adapts to the prevailing environmental conditions might influence epigenetic mechanisms and modulate gene expression. In this article, we put forward the idea that physical exercise, especially long-term repetitive strenuous exercise, positively affects health, reduces the aging process, and decreases the incidence of cancer through induced stress and epigenetic mechanisms. We pr…
Histone deacetylase inhibitors induce in human hepatoma HepG2 cells acetylation of p53 and histones in correlation with apoptotic effects
2007
This report shows that histone deacetylase inhibitors (HDACIs) induced apoptosis in human hepatoma HepG2 cells in a dose- and time-dependent manner. Trichostatin A (TSA), ITF2357 and suberoylanilide hydroxamic acid (SAHA), which were very effective agents, caused apoptotic effects after a lag phase of 12-16 h. In order to elucidate the mechanism of HDACIs action in HepG2 cells we have studied the effects of TSA, ITF2357 and SAHA on acetylation of p53 and histones H2A, H2B, H3 and H4. It was observed that HDACIs rapidly induced acetylation of these proteins, being the effects clearly visible already at 30 min of treatment at the same doses which caused apoptosis. Analysis of the immunocomple…
Histone-mediated transgenerational epigenetics
2019
Abstract Epigenetic mechanisms operate at the interface between the environment and genome, by converting the environmental stimuli to phenotypic responses through changes in the chromatin landscape, which ultimately affects gene expression in the absence of alterations in DNA sequence. In this scenario, transgenerational inheritance occurs when epigenetic variations induced by environmental stimuli are transmitted through the germ line to succeeding generations that had never experienced those stimuli. There is an ever-growing list of reports indicating that histones are fundamental players in these processes in a variety of organisms. In this chapter, we provide a perspective on histone-d…
Circulating histones contribute to monocyte and MDW alterations as common mediators in classical and COVID-19 sepsis
2022
Abstract Objective Histone proteins are physiologically involved in DNA packaging and gene regulation but are extracellularly released by neutrophil/monocyte extracellular traps and mediate thrombo-inflammatory pathways, associated to the severity of many human pathologies, including bacterial/fungal sepsis and COVID-19. Prominent and promising laboratory features in classic and viral sepsis emphasize monocyte distribution width (MDW), due to its ability to distinguish and stratify patients at higher risk of critical conditions or death. No data are available on the roles of histones as MDW modifiers. Design Comparison of MDW index was undertaken by routine hematology analyzer on whole bloo…
H3 and H3.3 histone mRNA amounts and ratio in oral squamous cell carcinoma and leukoplakia.
2006
Histone variants (e.g. H3) play an important role in chromatin structure and gene expression regulation of normal cells. Aims of this study were to: (1) estimate H3 and H3.3 histone mRNA expressions and their ratio in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL); (2) investigate whether H3 and H3.3 variants could play a role in the pathogenesis of OSCC and OL, also conditionally to HPV infection, age, gender, and main habits (tobacco smoking and alcohol drinking) in human beings studied. Twenty-three cases of OSCC and 20 cases of OL were examined in lesion site (LS) and juxtaposed clinically undamaged site (JUS) by RT-PCR for H3 and H3.3 histone mRNA; 13 healthy oral mucosa…
Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study
2021
Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the probability of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear proteins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological…
Developing rat brain as well as cultured astrocytes contain H1° mRNA-protein complexes
2015
RNA-binding proteins (RBPs) regulate intracellular transport, pre-localization, stability, and translation of mRNAs [1]. We previously identified a set of proteins which interact with mRNAs encoding H1° and H3.3 histones [2-5]. All these proteins are probably part of a ribonucleoprotein particle [6]. Here we report the results of a more detailed study on the expression and intracellular localization of some of these RBPs, such as hnRNP K and A1, and Hsc70, during rat brain development and in cultured rat astrocytes. We also investigated the presence in the complexes of PIPPin/CSD-C2 protein. Affinity chromatography was performed as already described [6]. Preparation of total lysates and cel…