Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation  

Overexpression of heme oxygenasel protects smooth muscle cells against oxidative injury and inhibits cell proliferation

作　　者：MIN ZHANG, BAO HuI ZHANG, LI CHEN, WEI AN1 Institute of Sports Medicine, The Third Hospital, Peking University, Beijing 100083, China 2Department of Cell Biology, Capital University of Medical Sciences, Beijing 100054, China 

出　　处：《Cell Research》2002年第2期123-132,共10页细胞研究（英文版）

基　　金：This work was kindly supported by Na-tional Natural Science Foundation of China(No.39670308)

摘　　要：To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.

关 键 词：Animals Blotting  Northern Blotting  Southern Blotting  Western Cell Division Cell Survival Cells  Cultured Cyclic GMP Dose-Response Relationship  Drug Flow Cytometry Free Radicals Genetic Vectors Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Humans Hydrogen Peroxide MAP Kinase Signaling System Male Membrane Proteins Muscle  Smooth Myocytes  Smooth Muscle OXIDANTS Oxidative Stress Oxygen Phosphorylation RATS Rats  Sprague-Dawley Research Support  Non-U.S. Gov't RETROVIRIDAE Time Factors Transfection 

分 类 号：Q25[生物学—细胞生物学]