Document Detail


Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways.
MedLine Citation:
PMID:  20669351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mesenchymal stem cell (MSC) transplantation has shown a therapeutic potential to repair the ischemic and infracted myocardium, but the effects are limited by the apoptosis and loss of donor cells in host cardiac microenvironment. The aim of this study is to explore the cytoprotection of heat shock protein 90 (Hsp90) against hypoxia and serum deprivation-induced apoptosis and the possible mechanisms in rat MSCs. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric analysis with annexin V/PI staining. The gene expression of Toll-like receptor-4 (TLR-4) and V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ErbB2) was detected by real-time polymerase chain reaction (PCR). The protein levels of cleaved caspase-3, Bcl-2, Bcl-xL, Bax, total-ERK, phospho-ERK, total-Akt, phospho-Akt, and Hsp90 were detected by Western blot. The production of nitric oxide was measured by spectrophotometric assay. Hsp90 improves MSC viability and protects MSCs against apoptosis induced by serum deprivation and hypoxia. The protective role of Hsp90 not only elevates Bcl-2/Bax and Bcl-xL/Bax expression and attenuates cleaved caspase-3 expression via down-regulating membrane TLR-4 and ErbB2 receptors and then activating their downstream PI3K/Akt and ERK1/2 pathways, but also enhances the paracrine effect of MSCs. These findings demonstrated a novel and effective treatment strategy against MSC apoptosis in cell transplantation.
Authors:
Feng Gao; Xin-yang Hu; Xiao-jie Xie; Qi-yuan Xu; Ya-ping Wang; Xian-bao Liu; Mei-xiang Xiang; Yong Sun; Jian-an Wang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of Zhejiang University. Science. B     Volume:  11     ISSN:  1862-1783     ISO Abbreviation:  J Zhejiang Univ Sci B     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-11-16     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101236535     Medline TA:  J Zhejiang Univ Sci B     Country:  China    
Other Details:
Languages:  eng     Pagination:  608-17     Citation Subset:  IM    
Affiliation:
Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia*
Apoptosis
Extracellular Signal-Regulated MAP Kinases / metabolism*
HSP90 Heat-Shock Proteins / metabolism*
Male
Mesenchymal Stromal Cells / cytology*
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Rats
Rats, Sprague-Dawley
Recombinant Proteins / chemistry
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells / cytology
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Chemical
Reg. No./Substance:
0/HSP90 Heat-Shock Proteins; 0/Recombinant Proteins; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
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