[Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways].
OBJECTIVE
To investigated the effect of lovastatin on hypoxia and serum deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated signaling pathway changes.


METHODS
MSCs were isolated from Sprague-Dawley rats. The anti-apoptotic effects of lovastatin were detected using Hoechst33342 and annexin V-FITC/PI binding assay by Flow cytometric analysis. The phosphorylation of Akt and ERK1/2, the cytochrome C and the cleaved caspase-3 were detected by Western blot.


RESULTS
Lovastatin (0.01 - 1 micromol/L) significantly reduced Hypoxia/SD-induced MSCs apoptosis and increased Akt phosphorylation, reduced caspase-3 activation and cytochrome c release from mitochondria to cytosol in a time dependent manner. These effects could be significantly blocked by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor, U0126.


CONCLUSIONS
Our results showed that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via activating PI3K/Akt and ERK1/2 signaling pathways suggesting a potential role of statins as an adjunct therapeutic agent during transplanting MSCs into damaged heart after myocardial infarction.
Xu
Rui-xia
RX
Research Center for Cardiovascular Regenerative Medicine, Ministry of Health, Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.
Chen
Xi
X
Hu
Sheng-shou
SS
Chen
Jing-hai
JH
Liu
Xue-wen
XW
Liu
Xue-bin
XB
Shi
Lin-hui
LH
Cong
Xiang-feng
XF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D045304:Cytochromes c; D008148:Lovastatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3