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Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.

ABSTRACT: Previously, we have found that changes in the location of intracellular heat shock protein (HSP)60 are associated with apoptosis. HSP60 has been reported to be a ligand of toll-like receptor (TLR)-4.We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR4.Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP60 induced apoptosis in cardiac myocytes, as detected by increased caspase 3 activity and increased DNA fragmentation. Apoptosis could be reduced by blocking antibodies to TLR4 and by nuclear factor kappaB binding decoys, but not completely inhibited, even though similar treatment blocked lipopolysaccharide-induced apoptosis. Three distinct controls showed no evidence for involvement of a ligand other than exHSP60 in the mediation of apoptosis.This is the first report of HSP60-induced apoptosis via the TLRs. HSP60-mediated activation of TLR4 may be a mechanism of myocyte loss in heart failure, where HSP60 has been detected in the plasma.

SUBMITTER: Kim SC

PROVIDER: S-EPMC2949276 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.

Kim Se-Chan SC Stice James P JP Chen Le L Jung James S JS Gupta Sanjiv S Wang Yin Y Baumgarten Georg G Trial Joann J Knowlton Anne A AA

Circulation research 20091029 12

<h4>Rationale</h4>Previously, we have found that changes in the location of intracellular heat shock protein (HSP)60 are associated with apoptosis. HSP60 has been reported to be a ligand of toll-like receptor (TLR)-4.<h4>Objective</h4>We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR4.<h4>Methods and results</h4>Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP ...[more]

PMID: 19875724

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Project description:BackgroundHelicobacter pylori (H. pylori) infection is a major risk factor for gastric diseases, including gastritis and gastric cancer. Heat shock protein 60 (HSP60) is a chaperone protein involved in various cellular processes and has been implicated in the immune response to bacterial infections. Extracellular vesicles (EVs) containing various protein components play important roles in cell communication. In the present study, a systematic proteomic analysis of EVs obtained from H. pylori infected cells was performed and the EV-derived HSP60 function was studied.MethodsEVs were evaluated by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The recognized protein components were quantified by label-free proteomics and subjected to bioinformatics assays. The expression of HSP60 in EVs, host cells and gastric cancers infected by H. pylori was determined by western blotting and immunohistochemical, respectively. In addition, the apoptotic regulation mechanisms of HSP60 in H. pylori infection were analyzed by western blotting and flow cytometry.ResultsA total of 120 important differential proteins were identified in the EVs from H. pylori-infected cells and subjected to Gene Ontology analysis. Among them, CD63, HSP-70 and TSG101 were verified via western blotting. Moreover, HSP60 expression was significantly increased in the EVs from H. pylori-infected GES-1 cells. H. pylori infection promoted an abnormal increase in HSP60 expression in GES-1 cells, AGS cells, gastric mucosa and gastric cancer. In addition, knockdown of HSP60 suppressed the apoptosis of infected cells and the expression of Bcl2, and promoted the upregulation of Bax.ConclusionThis study provides a comprehensive proteomic profile of EVs from H. pylori-infected cells, shedding light on the potential role of HSP60 in H. pylori infection. The findings underscore the significance of EV-derived HSP60 in the pathophysiology of H. pylori-associated diseases.

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Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.

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Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.

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