title: Angiotensin II degrades myeloid cell leukemia 1 in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, Shandong Province, China.
authors.forename: Ruyan
authors.initials: R
authors.lastname: Yang
authors.affiliation: Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, Shandong Province, China.
authors.forename: Yaorong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, Shandong Province, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Rong
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D013844:Thiazoles; D000804:Angiotensin II; C479831:N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea; D014508:Urea; D038362:Glycogen Synthase Kinase 3
keywords: angiotensin II; apoptosis; endothelial cells; myeloid cell leukemia 1 (Mcl-1)