https://scholars.lib.ntu.edu.tw/handle/123456789/445272
標題: | Cyclic strain-induced monocyte chemotactic protein-1 gene expression in endothelial cells involves reactive oxygen species activation of activator protein 1 | 作者: | Wung, B.S. Cheng, J.J. Hsieh, H.J. Shyy, Y.J. Wang, D.L. HSYUE-JEN HSIEH |
關鍵字: | Activator protein 1/tissue plasminogen activator-responsive element; Cyclic strain; Monocyte chemotactic protein- 1; Reactive oxygen species | 公開日期: | 1997 | 卷: | 81 | 期: | 1 | 起(迄)頁: | 1-7 | 來源出版物: | Circulation Research | 摘要: | Endothelial cells (ECs) are constantly exposed to blood pressure- induced mechanical strain. We have previously demonstrated that cyclic strain can induce gene expression of monocyte chemotactic protein-1 (MCP-1). The molecular mechanisms of gene induction by strain, however, remain unclear. Recent evidence indicates that intracellular reactive oxygen species (ROS) can act as a second messenger for signal transduction and thus affect gene expression. The potential role of ROS in strain-induced MCP-1 expression was investigated. ECs under cyclic strain induced a sustained elevated production of intracellular superoxide. ECs under strain or pretreated with either H2O2 or xanthine oxidase/hypoxanthine induced MCP-1 expression. Strain- or oxidant-induced MCP-1 mRNA levels could be inhibited by treating ECs with catalase or antioxidant N-acetyl-cysteine (NAC). Functional analysis of MCP- 1 promoter and site-specific mutations indicates that the proximal tissue plasminogen activator-responsive element (TRE) in the -60-bp promoter region is sufficient for strain or H2O2 inducibility. Electrophoretic mobility shift assays demonstrated an increase of nuclear proteins binding to TRE sequences from ECs subsequent to strain or H2O2 treatment. NAC or catalase pretreatment of ECs inhibited the strain- or H2O2-induced AP-1 binding. These results clearly indicate that cyclic strain inducibility of MCP-1 in ECs uses the interaction of AP-1 proteins with TRE sites via the elevation of intracellular ROS levels in strained ECs. These findings emphasize the importance of intracellular ROS in the modulation of hemodynamic force- induced gene expression in vascular ECs. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/445272 | DOI: | 10.1161/01.RES.81.1.1 | SDG/關鍵字: | acetylcysteine; catalase; hydrogen peroxide; hypoxanthine; messenger RNA; monocyte chemotactic protein 1; reactive oxygen metabolite; xanthine oxidase; article; atherosclerosis; blood vessel injury; cardiovascular disease; controlled study; endothelium cell; gene expression; hemodynamics; human; human cell; hypertension; mechanical stress; oxidative stress; plasminogen activation; priority journal; signal transduction |
顯示於: | 化學工程學系 |
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