DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: Activation of eNOS/NO and inhibition of Bax translocation
DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: Activation of eNOS/NO and inhibition of Bax translocation
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DOI：
10.1159/000149795
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Wang, Xiao-Ming
中科院分区：
文献类型：
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作者：
Liu, An-Heng;Cao, Ya-Nan;Wang, Xiao-Ming
目的：4,4'-二异硫氰芪-2,2'-二磺酸（DIDS）是一种非选择性氯通道阻滞剂，已被证明可以防止细胞凋亡，但其潜在机制仍不清楚，因此本研究旨在探讨磷脂酰肌醇3'-激酶（PI3K）/Akt及其下游分子是否参与细胞凋亡 DIDS 的细胞保护作用。方法：在存在或不存在 DIDS 的情况下，将新生大鼠心肌细胞暴露于星形孢菌素 (STS)。测定细胞活力、凋亡以及 Akt、磷酸化 Akt (p-Akt)、eNOS、磷酸化一氧化氮合酶 (p-eNOS)、Bcl-2/Bax 和一氧化氮 (NO) 的表达，并通过双重免疫荧光标记和蛋白质印迹评估 Bax 易位。结果：DIDS 显着提高了细胞活力，并对 STS 暴露的心肌细胞产生抗凋亡作用。 DIDS 导致 p-Akt 比对照水平增加 2.1 倍，防止 STS 导致的 eNOS 表达和磷酸化 eNOS 水平降低，并显着增加 NO 产生（所有 P
Aims: 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a non-selective chloride channel blocker, has been shown to prevent cell apoptosis, however, the underlying mechanisms remain undefined, thus the present study was to explore whether phosphatidylinositol 3'-kinase (PI3K)/Akt and its downstream molecules are involved in the cytoprotective effect of DIDS. Methods: Neonatal rat cardiomyocytes were exposed to staurosporine (STS) in the presence or absence of DIDS. Cell viability, apoptosis and expressions of Akt, phospho-Akt (p-Akt), eNOS, phospho-eNOS (p-eNOS), Bcl-2/Bax and nitric oxide (NO) production were determined, and Bax translocation was assessed by double immunofluorescence labeling and Western blotting. Results: DIDS markedly improved cell viability and exerted an anti-apoptotic effect on STS-exposed cardiomyocytes. DIDS resulted in a 2.1-fold increase of p-Akt over control levels, prevented the reduction in eNOS expression and phospho-eNOS levels by STS and significantly increased NO production (all P