title: [Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways].
abstract: 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.
authors.affiliation: 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.
authors.forename: Rui-xia
authors.initials: RX
authors.lastname: Xu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Sheng-shou
authors.initials: SS
authors.lastname: Hu
authors.forename: Jing-hai
authors.initials: JH
authors.lastname: Chen
authors.forename: Xue-wen
authors.initials: XW
authors.lastname: Liu
authors.forename: Xue-bin
authors.initials: XB
authors.lastname: Liu
authors.forename: Lin-hui
authors.initials: LH
authors.lastname: Shi
authors.forename: Xiang-feng
authors.initials: XF
authors.lastname: Cong
mesh_terms: 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*
chemical_list: D045304:Cytochromes c; D008148:Lovastatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3