Nrf2 is involved in the effect of tanshinone IIA on intracellular redox status in human aortic smooth muscle cells.
Tanshinone IIA is the major antioxidant component in the traditional Chinese medicine Salvia miltiorrhiza. Transcription factor nuclear-factor-E2-related factor (Nrf2) regulates a battery of antioxidant response element (ARE)-regulated genes. The aim of this study was to determine the effect of tanshinone IIA on Nrf2 activation and intracellular redox status in human aortic smooth muscle cells. Tanshinone IIA potentiated tumor necrosis factor alpha (TNF-alpha)-mediated nuclear accumulation of Nrf2 and expression of ARE-related genes, while it reversed TNF-alpha-induced down-regulation of intracellular glutathione (GSH), NADPH and glucose 6-phosphate dehydrogenase (G6PDH) levels. Specific silence of Nrf2 by siRNA down-regulated tanshinone IIA-induced Nrf2 activation and increased of intracellular GSH, NADPH and G6PDH levels. Tanshinone IIA-induced Nrf2 activation was association with activation of ERK and PKB, which was prevented by treatment with PD098059 or wortmannin. Tanshinone IIA attenuated TNF-alpha, angiotensin II, H(2)O(2)-mediated reactive oxygen species (ROS) production. These results demonstrated that tanshinone IIA-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress via ERK and PKB signaling pathways.
Zhang
Hong-Sheng
HS
Department of Biotechnology, Beijing Institute of Radiation Medicine, Taiping Road 27#, Haidian District, Beijing 100850, China.
Wang
Sheng-Qi
SQ
D045784:Abietanes; D000217:Acyltransferases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D001011:Aorta / Q000166:cytology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D045784:Abietanes; D051267:NF-E2-Related Factor 2; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C021751:tanshinone; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D000217:Acyltransferases; C057250:acyl-CoA-independent retinyl ester synthetase