PMID- 20669351
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20211020
IS  - 1862-1783 (Electronic)
IS  - 1673-1581 (Print)
IS  - 1673-1581 (Linking)
VI  - 11
IP  - 8
DP  - 2010 Aug
TI  - Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and 
      serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways.
PG  - 608-17
LID - 10.1631/jzus.B1001007 [doi]
AB  - 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.
FAU - Gao, Feng
AU  - Gao F
AD  - Department of Cardiology, the Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Hu, Xin-yang
AU  - Hu XY
FAU - Xie, Xiao-jie
AU  - Xie XJ
FAU - Xu, Qi-yuan
AU  - Xu QY
FAU - Wang, Ya-ping
AU  - Wang YP
FAU - Liu, Xian-bao
AU  - Liu XB
FAU - Xiang, Mei-xiang
AU  - Xiang MX
FAU - Sun, Yong
AU  - Sun Y
FAU - Wang, Jian-an
AU  - Wang JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - J Zhejiang Univ Sci B
JT  - Journal of Zhejiang University. Science. B
JID - 101236535
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - *Hypoxia
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/chemistry
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cells/cytology
MH  - Tetrazolium Salts/pharmacology
MH  - Thiazoles/pharmacology
PMC - PMC2916094
EDAT- 2010/07/30 06:00
MHDA- 2010/11/17 06:00
PMCR- 2010/08/01
CRDT- 2010/07/30 06:00
PHST- 2010/07/30 06:00 [entrez]
PHST- 2010/07/30 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 10.1631/jzus.B1001007 [doi]
PST - ppublish
SO  - J Zhejiang Univ Sci B. 2010 Aug;11(8):608-17. doi: 10.1631/jzus.B1001007.