Ursodeoxycholic acid can suppress deoxycholic acid-induced apoptosis by stimulating Akt/PKB-dependent survival signaling
Ursodeoxycholic acid can suppress deoxycholic acid-induced apoptosis by stimulating Akt/PKB-dependent survival signaling
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DOI：
10.1207/s15327914nc5101_15
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Martinez, JD
中科院分区：
文献类型：
--
作者：
Im, E;Akare, S;Martinez, JD
据报道，无毒胆汁酸熊去氧胆酸（UDCA）是一种抗凋亡药物，对多种死亡刺激有效，包括细胞毒性胆汁酸去氧胆酸（DCA）。为了深入了解这种抗凋亡特性，我们测试了UDCA保护结肠癌衍生细胞系HCT116免受dca诱导的细胞凋亡的能力。我们发现UDCA能够以时间和剂量依赖的方式抑制dca诱导的细胞凋亡，并且这种作用与Akt磷酸化相关。重要的是，当Akt活性被显性负Akt突变体抑制或PI3K活性被药理学抑制时，UDCA失去了保护细胞免受dca诱导的细胞死亡的能力。这些结果表明，UDCA可以通过刺激akt依赖的存活信号来保护HCT116细胞免受dca诱导的凋亡。
The nontoxic bile acid ursodeoxycholic acid (UDCA) is reported to be an anti-apoptotic agent with efficacy against a variety of death stimuli including the cytotoxic bile acid deoxycholic acid (DCA). To gain insight into this anti-apoptotic property, we tested UDCA for its ability to protect the colon carcinoma-derived cell line HCT116 against DCA-induced apoptosis. We found that UDCA could suppress DCA-induced apoptosis in a time- and dose-dependent manner and that this effect correlated with Akt phosphorylation. Importantly, UDCA lost its ability to protect cells from DCA-induced cell death when Akt activity was suppressed genetically using a dominant negative Akt mutant or when PI3K activity was inhibited pharmacologically. These results suggest that UDCA can protect HCT116 cells against DCA-induced apoptosis by stimulating Akt-dependent survival signaling.