title: Gallic acid attenuates oleic acid-induced proliferation of vascular smooth muscle cell through regulation of AMPK-eNOS-FAS signaling.
abstract: Vascular smooth muscle cell (VSMC) proliferation plays a central role in the pathogenesis of obesity-related atherosclerosis. The molecular mechanism of GA on oleic acid (OA)-induced proliferation of vascular smooth muscle cell is evaluated. Cells were treated with OA (150 μM), or co-treated with OA and GA (10-30 μM) for 48 h, MTT assay was performed for proliferation. Using flow cytometry analysis, the GA-treated cells caused an increase in G2/M phase. A decrease in cyclin B1 and cyclin-dependent kinase 1 (cdc2) and increase in kip/p27 and cip1/p21 were found by western blotting. Additional mechanistic studies showed that GA induced the activation of AMP-activated protein kinase (AMPK) and eNOS and the inhibition of fatty acid synthase (FAS) after stimulation with OA. Furthermore, the addition of compound C, a specific inhibitor of AMPK, reduced the activation of GA-mediated eNOS and NO production and increased the proliferation of cells. Inhibition of NOS by L-NAME had no further effect on VSMC proliferation. The present results indicate that GA was an effected and anti-atherogenic agent in VSMC. It attenuates cell cycle progression via AMPKmediated eNOS activation, which results in the production of NO and prevents atherosclerosis.
authors.affiliation: Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.. wcj@csmu.edu.tw.
authors.forename: Ting-Tsz
authors.initials: TT
authors.lastname: Ou
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lin
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Wu
authors.forename: Wea-Lung
authors.initials: WL
authors.lastname: Lin
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019301:Oleic Acid; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats
chemical_list: D020011:Protective Agents; D019301:Oleic Acid; D009569:Nitric Oxide; D005707:Gallic Acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D054890:Fatty Acid Synthase, Type I; D055372:AMP-Activated Protein Kinases