title: Genistein ameliorated endothelial nitric oxidase synthase uncoupling by stimulating sirtuin-1 pathway in ox-LDL-injured HUVECs.
abstract: Endothelial nitric oxidase synthase (eNOS) uncoupling plays a causal role in endothelial dysfunction in atherosclerosis. Genistein consumption has been associated with the prevention of atherosclerosis. However, the effect of genistein on eNOS uncoupling has not been reported. A model of oxidized low-density lipoprotein (ox-LDL)-induced injury on human umbilical vein endothelial cells (HUVECs) was established to evaluate the effect of genistein on eNOS uncoupling. We investigated the effect of genistein on NADPH oxidase-dependent superoxide production, NOX4 expression, BH4 synthesis and oxidation, the expression of GTP cyclohydrolase 1 (GCH1) and dihydrofolate reductase (DHFR). The results showed that genistein decreased superoxide production and NOX4 expression, enhanced the ratio of BH4/BH2, augmented the expressions of GCH1 and DHFR. Accompanied with genistein ameliorating eNOS uncoupling, genistein elevated the expression of sirtuin-1; furthermore, the effects of genistein on eNOS uncoupling were blunted with sirtuin-1 siRNA. The present study indicated that genistein ameliorated eNOS uncoupling was concerned with sirtuin-1 pathway in ox-LDL-injured HUVECs.
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: hpzhang7302@aliyun.com.
authors.forename: Hua-ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Jia-hui
authors.initials: JH
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Hai-xia
authors.initials: HX
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Dong-xing
authors.initials: DX
authors.lastname: Guo
mesh_terms: D006136:GTP Cyclohydrolase / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; C099252:oxidized low density lipoprotein; D013481:Superoxides; D019833:Genistein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D056564:Sirtuin 1; D006136:GTP Cyclohydrolase
keywords: Atherosclerosis; Genistein; Sirtuin-1; eNOS uncoupling