Genistein ameliorated endothelial nitric oxidase synthase uncoupling by stimulating sirtuin-1 pathway in ox-LDL-injured HUVECs
| Autor: | Yu Haixia, Jia-hui Zhao, Huaping Zhang, Dong-xing Guo |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nitric Oxide Synthase Type III Health Toxicology and Mutagenesis Genistein 030204 cardiovascular system & hematology Biology Toxicology Umbilical vein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sirtuin 1 Superoxides Enos Internal medicine Human Umbilical Vein Endothelial Cells medicine Humans heterocyclic compounds Endothelial dysfunction GTP Cyclohydrolase Protein Kinase Inhibitors Pharmacology Oxidase test Superoxide food and beverages NOX4 General Medicine medicine.disease biology.organism_classification Lipoproteins LDL 030104 developmental biology Endocrinology chemistry biology.protein |
| Zdroj: | Environmental Toxicology and Pharmacology. 42:118-124 |
| ISSN: | 1382-6689 |
| DOI: | 10.1016/j.etap.2016.01.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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