Arsenic induces peroxynitrite generation and cyclooxygenase-2 protein expression in aortic endothelial cells: Possible role in atherosclerosis

被引:72
作者
Bunderson, M
Coffin, JD
Beall, HD [1 ]
机构
[1] Univ Montana, Dept Pharmaceut Sci, Missoula, MT 59812 USA
[2] Univ Montana, Environm Hlth Sci Ctr, Missoula, MT 59812 USA
关键词
arsenic; arsenite; endothelial cells; peroxynitrite; nitrotyrosine; cyclooxygenase-2; atherosclerosis; prostaglandins;
D O I
10.1006/taap.2002.9492
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Epidemiological evidence suggests that exposure to the metalloid arsenic constitutes a risk factor for cardiovascular disease. The purpose of this study was to determine whether arsenic could stimulate generation of factors involved in oxidative stress and inflammation, conditions associated with atherosclerosis, or coronary artery disease. We found that production of peroxynitrite, a strong oxidant formed from the coupling of nitric oxide and superoxide anion, was significantly increased in bovine aortic endothelial (BAE) cells exposed to sodium arsenite at concentrations as low as 0.5 muM. Expression of the inflammatory mediator cyclooxygenase-2 (COX-2) was also upregulated in response to arsenite exposure as demonstrated by Western blot analysis. The increase in COX-2 protein was time dependent with highest levels at 30 min and 48 h. This result was supported by an increase in the generation of prostaglandin E-2, following exposure to arsenic. Nitrotyrosine residues in proteins are indicative of peroxynitrite generation, and extensive nitrotyrosine formation has been detected in atherosclerotic plaques. Therefore, COX-2 protein was immunoprecipitated from BAE cells and submitted to Western blot analysis using an antibody to nitrotyrosine. Nitration of COX-2 was detected in arsenic-treated cells, but not in untreated control cells. The findings in this report suggest an increase in reactive species, notably peroxynitrite, in BAE cells exposed to arsenic. Furthermore, induction of important inflammatory mediators such as COX-2 may exacerbate the inflammatory state typical of atherosclerosis. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:11 / 18
页数:8
相关论文
共 43 条
[1]   Arsenic: Health effects, mechanisms of actions, and research issues [J].
Abernathy, CO ;
Liu, YP ;
Longfellow, D ;
Aposhian, HV ;
Beck, B ;
Fowler, B ;
Goyer, R ;
Menzer, R ;
Rossman, T ;
Thompson, C ;
Waalkes, M .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1999, 107 (07) :593-597
[2]   Intracellular generation of reactive oxygen species during nonhypoxic lung ischemia [J].
AlMehdi, AB ;
Shuman, H ;
Fisher, AB .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1997, 272 (02) :L294-L300
[3]   Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite [J].
Barchowsky, A ;
Klei, LR ;
Dudek, EJ ;
Swartz, HM ;
James, PE .
FREE RADICAL BIOLOGY AND MEDICINE, 1999, 27 (11-12) :1405-1412
[4]   Oxidative damage and tyrosine nitration from peroxynitrite [J].
Beckman, JS .
CHEMICAL RESEARCH IN TOXICOLOGY, 1996, 9 (05) :836-844
[5]  
Beckman JS, 1996, AM J PHYSIOL-CELL PH, V271, pC1424
[6]   EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY [J].
BECKMANN, JS ;
YE, YZ ;
ANDERSON, PG ;
CHEN, J ;
ACCAVITTI, MA ;
TARPEY, MM ;
WHITE, CR ;
BECKMAN, JS .
BIOLOGICAL CHEMISTRY HOPPE-SEYLER, 1994, 375 (02) :81-88
[7]  
Boulos C, 2000, J PHARMACOL EXP THER, V293, P222
[8]   Clues and uncertainties in in the risk assessment of arsenic in drinking water [J].
Buchet, JP ;
Lison, D .
FOOD AND CHEMICAL TOXICOLOGY, 2000, 38 :S81-S85
[9]   Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo [J].
Cheng, XS ;
Shimokawa, H ;
Momii, H ;
Oyama, J ;
Fukuyama, N ;
Egashira, K ;
Nakazawa, H ;
Takeshita, A .
CARDIOVASCULAR RESEARCH, 1999, 42 (03) :651-659
[10]   COX-2 and the cyclopentenone prostaglandins - a new chapter in the book of inflammation? [J].
Colville-Nash, PR ;
Gilroy, DW .
PROSTAGLANDINS & OTHER LIPID MEDIATORS, 2000, 62 (01) :33-43