Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways
Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways
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DOI：
10.1016/j.ejphar.2010.08.060
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发表时间：
2010-12-15
影响因子：
5
通讯作者：
Ye, Zuguang
中科院分区：
文献类型：
--
作者：
Li, Chunmei;Tian, Jingwei;Ye, Zuguang
心肌细胞凋亡在心脏病的发生发展中起着重要作用。从川续断中提取的三萜皂苷--诱导心肌细胞凋亡心肌细胞暴露于缺氧条件下6小时，然后细胞活力显着降低，培养上清液中乳酸脱氢酶（LDH）和肌酸磷酸激酶（CK）活性显着增加缺氧激活的细胞凋亡通过Hoechst 33258核染色和Annexin V-证实。FITC染色这些变化与Bcl-2/Bax比值的降低、活性caspase 3表达、Akt和cAMP反应元件结合蛋白（CREB）的磷酸化有关。此外，阿萨VI以剂量依赖性方式显著减弱了缺氧处理的心肌细胞中LDH和CK活性的升高，并增加了细胞活力。FITC染色结果显示，阿萨VI处理可通过增加Bcl 2/Bax比值，降低caspase 3活性表达，增加pAkt和p-Akt表达，抑制缺氧诱导的心肌细胞凋亡。此外，阿萨VI的保护作用可被磷脂酰肌醇-3-激酶（PI 3 K）抑制剂LY 294002阻断。因此，我们证明阿萨VI对缺氧诱导的心肌细胞凋亡具有保护作用，可能是通过激活PI 3 K/PI 3 K通路。Akt和CREB通路（C）2010 Elsevier B V保留所有权利
Cardiomyocyte apoptosis plays a critical role in the progress of heart diseases Asperosaponin VI (ASA VI) a triterpene saponin isolated from Dipsacus asper Wall has shown cardioprotective effects in vivo However whether ASA VI has a protective effect against cardiomyocyte apoptosis is poorly understood The present study was aimed to investigate the cardioprotective role of ASA VI and the underlying mechanisms in hypoxia-induced cardiomyocyte apoptosis Cardiomyocytes were exposed to hypoxic condition for 6 h and then cell viability markedly decreased lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities in the culture supernatant significantly increased Hypoxia-activated apoptosis were confirmed by Hoechst 33258 nuclear staining and Annexin V-FITC staining These changes were associated with the decrease of the Bcl-2/Bax ratio active caspase 3 expression phosphorylations of Akt and cAMP response element-binding protein (CREB) Moreover ASA VI significantly attenuated increased LDH and CK activities and increased cell viability in hypoxia treated myocytes in a dose-dependent fashion Hoechst 33258 nuclear staining and Annexin V-FITC staining observations demonstrated the same protective effects ASA VI treatment inhibited apoptosis in hypoxia-induced cardiomyocyte by increasing the Bcl 2/Bax ratio and decreasing active caspase 3 expression as well enhancing of p Akt and p-CREB Furthermore the protective effects of ASA VI were prevented by phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 treatment In consequence we demonstrated that ASA VI had protective effect against hypoxia induced cardiomyocytes apoptosis probably by activating the PI3K/Akt and CREB pathways (C) 2010 Elsevier B V All rights reserved