title: Identification of Cofilin-1 Induces G0/G1 Arrest and Autophagy in Angiotensin-(1-7)-treated Human Aortic Endothelial Cells from iTRAQ Quantitative Proteomics.
abstract: The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis is a pathway that acts against the detrimental effects of the renin-angiotensin system. However, the effects of angiotensin-(1-7) on endothelial protein expression and the related phenotypes are unclear. We performed a duplicate of iTRAQ quantitative proteomic analysis on human aortic endothelial cells (HAECs) treated with angiotensin-(1-7) for 6 hours. Cofilin-1 was identified as a highly abundant candidate with consistent >30% coverage and >1.2-fold overexpression in the angiotensin-(1-7)-treated group. Gene ontology analysis showed that the "regulation_of_mitosis" was significantly altered, and cell cycle analysis indicated that the 6-hour angiotensin-(1-7) treatment significantly induced G0/G1 arrest. Knockdown of the cofilin-1 (CFL1) gene suggested the G0/G1 phase arrest was mediated by the modulation of p27 and the p21/Cyclin/CDK complex by Cofilin-1. Interestingly, quiescent HAECs escaped G0/G1 arrest upon angiotensin-(1-7) treatment for 24 hours, and angiotensin-(1-7) induced autophagy by upregulating Beclin-1 and microtubule-associated protein 1 light chain 3b-II expression, which was also attenuated by A779 pre-treatment and CFL1 knockdown. After pre-treatment with 3-methyladenine (3MA), treatment with angiotensin-(1-7) for 24 h induced significant G0/G1 phase arrest and apoptosis, suggesting a pro-survival role of autophagy in this context. In conclusion, Cofilin-1 plays a dominant role in angiotensin-(1-7)-induced G0/G1 arrest and autophagy to maintain cellular homeostasis in HAECs.
authors.affiliation: School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C.|Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung Taiwan 40447, R.O.C.|Cardiovascular Research Laboratory, China Medical University Hospital, No. 2, Yude Road, Taichung Taiwan 40447, R.O.C.
authors.forename: Huang-Joe
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Chemistry, National Taiwan Normal University, No. 88, Sec. 4, Ting-Chow Rd, Taipei, Taiwan 11677, R.O.C.
authors.forename: Sung-Fang
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Cardiovascular &Translational Medicine Laboratory, Department of Biotechnology, Hung Kuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung Taiwan 43302, R.O.C.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Lo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D000803:Angiotensin I / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology*; D017209:Apoptosis; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000032:analysis*; D004730:Endothelium, Vascular / Q000473:pathology*; D016193:G1 Phase; D020868:Gene Silencing; D006706:Homeostasis; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D016192:Resting Phase, Cell Cycle
chemical_list: D015415:Biomarkers; C495810:CFL1 protein, human; D051338:Cofilin 1; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C025946:3-methyladenine; D000803:Angiotensin I; C118790:angiotensin I (1-7); D000225:Adenine