Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigated the effect of lovastatin on hypoxia and serum deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated signaling pathway changes.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>