title: Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced             apoptosis by activating the PI3K/Akt and CREB pathways.
abstract: Picroside II, an iridoid glucoside found in the root of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to reduce apoptosis in neuronal cells and other cell types. However, whether picroside II has a protective effect against cardiomyocyte apoptosis is poorly understood. In the present study, we investigated the cardioprotective role of picroside II and the underlying mechanisms in hypoxia/reoxygenation-induced cardiomyocyte apoptosis. The pretreatment with picroside II markedly attenuated hypoxia/reoxygenation-induced cell damage dose-dependently, which was evident by the increased cell viability and the corresponding decrease in lactate dehydrogenase release (LDH). The pretreatment with picroside II inhibited apoptosis confirmed by Annexin V-FITC staining, Hoechst 33258 nuclear staining and by assessment of caspase-3 activity. In addition, we found that picroside II not only increased the expression of Bcl-2, while decreasing Bax expression, but also augmented Akt and cAMP response element-binding protein (CREB) phosphorylation and ultimately inhibited hypoxia/reoxygenation-induced apoptosis. Furthermore, the protective effects of picroside II were abrogated by pretreatment of the cells with wortmannin or LY294002, a specific PI3K inhibitor. The present study suggests that picroside II inhibits hypoxia/reoxygenation-induced apoptosis in cardiomyocytes by activating the PI3K/Akt and CREB pathways and modulating expression of Bcl-2 and Bax.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China. fanjimeng2060@yahoo.cn
authors.forename: Fan-Ji
authors.initials: FJ
authors.lastname: Meng
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Jiao
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D057888:Iridoid Glucosides / Q000737:chemistry / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002934:Cinnamates; D017362:Cyclic AMP Response Element-Binding Protein; D057888:Iridoid Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C416837:picroside II; D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt