Proteasome-dependent inactivation of Akt is essential for 12-O-tetradecanoylphorbol 13-acetate-induced apoptosis in vascular smooth muscle cells
Proteasome-dependent inactivation of Akt is essential for 12-O-tetradecanoylphorbol 13-acetate-induced apoptosis in vascular smooth muscle cells
复制标题
蛋白酶体依赖性 Akt 失活对于 12-O-十四烷酰佛波醇 13-乙酸酯诱导血管平滑肌细胞凋亡至关重要
DOI：
10.1007/s10495-008-0272-z
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发表时间：
2008-12-01
期刊：
影响因子：
7.2
通讯作者：
Li, HuiHua
中科院分区：
文献类型：
--
作者：
Fan, Yongna;Xie, Ping;Li, HuiHua
血管平滑肌细胞(SMC)的凋亡是血管重塑的重要特征。我们研究了12-O-十四酰佛波醇13-乙酸酯(TPA)对SMC凋亡的影响。我们发现TPA通过快速下调Akt的磷酸化来诱导SMC的凋亡。TPA对Akt激活的抑制作用可被蛋白磷酸酶2A和蛋白酶体抑制剂明显减弱。此外，TPA促进了p-Akt的泛素化，而抑制TPA诱导的PKC激活抑制了p-Akt的下调和泛素化。综上所述，这些结果表明，TPA至少部分地通过PKC和泛素-蛋白酶体的降解触发Akt的失活，从而促进SMC的凋亡。
Apoptosis of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling. Here we investigated the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on SMC apoptosis. We found that TPA treatment induced SMC apoptosis through the rapid downregulation of Akt phosphorylation. The inhibition of Akt activation by TPA was markedly reduced by inhibitors of protein phosphatase 2A and proteasome. Moreover, TPA promoted the ubiquitination of p-Akt, whereas inhibition of TPA-induced PKC activation suppressed the downregulation and ubiquitination of p-Akt. Taken together, these results demonstrate that TPA triggers inactivation of Akt, at least in part, through PKC and Ubiquitin–proteasome degradation, thereby contributing to SMC apoptosis.