Redox-sensitive regulation of lox-1 gene expression in vascular endothelium.
Oxidative stress has been implicated in atherosclerosis and its underlying conditions. LOX-1 is a novel endothelial receptor for oxidized low-density lipoprotein which might mediate endothelial dysfunction and subsequent atherogenesis. In the present study, we examined LOX-1 gene regulation by oxidative stress. First, superoxide anions generated by hypoxanthine and xanthine oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in cultured aortic endothelial cells. Homocysteine, an atherogenic substance believed to exert its effects through oxidative stress, enhanced endothelial LOX-1 gene expression, which was suppressed by N-acetylcysteine. Second, rats receiving angiotensin II for 10 days manifested hypertension and LOX-1 upregulation in aortic endothelium via AT1 receptor. Tempo, a superoxide dismutase mimetic, alleviated LOX-1 augmentation induced by angiotensin II. These results indicated redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems, suggesting its potential role in atherosclerosis.
Nagase
M
M
Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Bunkyo-ku, 112-8688, Japan. mnagase-tky@umin.ac.jp
Ando
K
K
Nagase
T
T
Kaname
S
S
Sawamura
T
T
Fujita
T
T
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006710:Homocysteine / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
C495136:OLR1 protein, rat; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D006710:Homocysteine; D000804:Angiotensin II