Tanshinone IIA attenuates cyclic strain-induced endothelin-1 expression in human umbilical vein endothelial cells

Hong Jye Hong, Feng Lin Hsu, Shih Chang Tsai, Cheng Hsin Lin, Ju Chi Liu, Jin Jer Chen, Tzu Hurng Cheng, Paul Chan

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

1. Tanshinone IIA, one of the active components of the Radix of Salvia miltiorrhiza, is used in traditional Chinese medicine to treat cardiovascular diseases. However, the intracellular mechanism of action of tanshinone IIA remain to be determined. The aims of the present study were to test the hypothesis that tanshinone IIA alters strain-induced endothelin (ET)-1 expression and nitric oxide (NO) production, as well as to identify the putative signalling pathways involved, in human umbilical vein endothelial cells (HUVEC). 2. Cultured HUVEC were exposed to cyclic strain in the presence of 1-10μmol/L tanshinone IIA. Expression of ET-1 was examined by reverse transcription-polymerase chain reaction and ELISA. Phosphorylation of endothelial NO synthase (eNOS) and activating transcription factor (ATF) 3 was assessed by western blot analysis. 3. Tanshinone IIA (3 and 10μmol/L) inhibited strain-induced ET-1 expression. In contrast, NO production, eNOS phosphorylation and ATF3 expression were enhanced by tanshinone IIA. The eNOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 100μmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (5 μmol/L) and the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; 10 μmol/L) inhibited tanshinone IIA-induced increases in ATF3 expression. Moreover, treatment of HUVEC with either an NO donor (3,3-bis [aminoethyl]-1-hydroxy-2-oxo-1-triazene; 500 μmol/L) or an ATF3 activator (carbobenzoxy-l-leucyl-l-leucyl-l-leucinal; 5μmol/L) resulted in the repression of strain-induced ET-1 expression. The inhibitory effect of tanshinone IIA on strain-induced ET-1 expression was significantly attenuated by l-NAME, ODQ and the transfection of small interfering RNA for ATF3. 4. In conclusion, tanshinone IIA inhibits strain-induced ET-1 expression by increasing NO and upregulating ATF3 in HUVEC. The present study provides important new insights into the molecular pathways that may contribute to the beneficial effects of tanshinone IIA in the cardiovascular system.
原文英語
頁(從 - 到)63-68
頁數6
期刊Clinical and Experimental Pharmacology and Physiology
39
發行號1
DOIs
出版狀態已發佈 - 一月 2012

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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