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Proteasome-dependent inactivation of Akt is essential for 12-O-tetradecanoylphorbol 13-acetate-induced apoptosis in vascular smooth muscle cells

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A Correction to this article was published on 27 November 2021

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Abstract

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.

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Acknowledgments

This work was supported by grants from China Natural Science Foundation (H. L., 2006CB503800, 2006CB910306, 30670860, 20060023051, and 20070023022).

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Authors and Affiliations

  1. Department of Pathology and National Laboratory of Medical Molecular Biology, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Tsinghua University, Beijing, 100005, China

    Yongna Fan, Ping Xie, Hua Zhang, Mingpeng She & HuiHua Li

  2. Department of Acute Medicine, Peking Union Medical Hospital, Beijing, China

    Shubin Guo

  3. Division of Population Genetics and Prevention, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China

    Dongfeng Gu

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  1. Yongna Fan
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  2. Ping Xie
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Correspondence to HuiHua Li.

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Fan, Y., Xie, P., Zhang, H. et al. Proteasome-dependent inactivation of Akt is essential for 12-O-tetradecanoylphorbol 13-acetate-induced apoptosis in vascular smooth muscle cells. Apoptosis 13, 1401–1409 (2008). https://doi.org/10.1007/s10495-008-0272-z

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  • DOI: https://doi.org/10.1007/s10495-008-0272-z

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