Open AccessHypoxic preconditioning attenuates hypoxia/reoxygenation‐induced apoptosis in mesenchymal stem cells 1
Author(s) -
WANG Jianan,
CHEN Tielong,
JIANG Jun,
SHI Heng,
GUI Chun,
LUO Ronghua,
XIE Xiaojie,
XIANG Meixiang,
ZHANG Xing
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00716.x
Subject(s) - protein kinase b , mesenchymal stem cell , apoptosis , mapk/erk pathway , viability assay , hypoxia (environmental) , vascular endothelial growth factor , microbiology and biotechnology , stem cell , phosphorylation , transplantation , vascular endothelial growth factor a , kinase , biology , pharmacology , chemistry , cancer research , medicine , biochemistry , vegf receptors , organic chemistry , oxygen
Aim : Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia‐reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation‐induced apoptosis of MSC. Methods : Three generations of MSC were divided into 6 groups, including the normal group, hypoxia‐reoxygenation (H/R) group, cyclosporine A (CsA), and the HPC 10 min, 20 min, and 30 min groups. The apoptotic index, cell viability, mitochondrial membrane potential, translocation of Bcl‐2 and bax, extracellular regulated kinase (ERK), Akt, hypoxia‐inducible factor 1‐α, and the vascular endothelial growth factor (VEGF) were tested after H/R treatment. Results : HPC decreased the apoptotic index and increased the viability induced by H/R. Moreover, HPC markedly stabilized mitochondrial membrane potential, upregulated Bcl‐2 and VEGF expressions, and increased the phosphorylation of ERK and Akt. As a positive control, CsA has the same function as HPC, except for promoting ERK and Akt phosphorylation and upregulating VEGF. Conclusion : HPC had a protective effect against MSC apoptosis induced by H/R via stabilizing mitochondrial membrane potential, upregulating Bcl‐2 and VEGF, and promoting ERK and Akt phosphorylation. HPC has implications for the development of novel stem cell protective strategies.