Angiotensin II (Ang II) plays a central role in cardiovascular diseases by causing endothelial apoptosis and dysfunction. Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of apoptosis-regulating proteins. It has been reported that Mcl-1 plays a pivotal role in protecting cells against apoptosis. Presently, the effects of Ang II on the expression of Mcl-1 remain unknown. In this study, we report, for the first time, that the antiapoptotic protein Mcl-1 is degraded by the proteasome during Ang II-induced apoptosis in HUVECs. Notably, our results demonstrate that prior phosphorylation by GSK-3β is required for proteasomal degradation of Mcl-1. Notably, the reduced level of Mcl-1 was abolished by a specific GSK-3β inhibitor, suggesting that the phosphorylation of Mcl-1 by GSK-3β is required for proteasomal degradation of Mcl-1. Overexpression of Mcl-1 rescued apoptosis induced by Ang II, however, knockdown of Mcl-1 exacerbated Ang II-induced apoptosis, thereby indicating that the protein level of Mcl-1 determines the response of endothelial cells to this drug. © 2017 IUBMB Life, 69(5):321-327, 2017.
Keywords: angiotensin II; apoptosis; endothelial cells; myeloid cell leukemia 1 (Mcl-1).
© 2017 International Union of Biochemistry and Molecular Biology.