Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase

被引:192
作者
Zou, MH [1 ]
Ullrich, V [1 ]
机构
[1] UNIV KONSTANZ,FAC BIOL,D-78434 CONSTANCE,GERMANY
关键词
peroxynitrite; hypochlorite; prostacyclin synthase; ischemia-reperfusion; irreversible inhibition; circulation;
D O I
10.1016/0014-5793(96)00160-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of various oxidants on bovine aortic prostacyclin synthase was tested with C-14-labelled prostaglandin endoperoxide as substrate, No sensitivity against hydrogen peroxide, superoxide or hydroxyl radicals was observed but hypochlorite inhibited with an IC50 value of 7 mu M. Among the reactive nitrogen species nitric oxide and nitrogen dioxide radicals were ineffective, but peroxynitrite irreversibly blocked prostacyclin biosynthesis with an IC50 value of 50 nM. Peroxynitrite acted within seconds whereas hypochlorite required up to 30 min for completion, Simultaneous generation of nitric oxide and superoxide also caused inhibition which suggested that under pathological conditions like ischemia-reperfusion not only the vasodilatory effects of nitric oxide but also those of prostacyclin could be eliminated.
引用
收藏
页码:101 / 104
页数:4
相关论文
共 17 条
[1]   PATHOLOGICAL IMPLICATIONS OF NITRIC-OXIDE, SUPEROXIDE AND PEROXYNITRITE FORMATION [J].
BECKMAN, JS ;
CROW, JP .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (02) :330-334
[2]  
CASTRO L, 1994, J BIOL CHEM, V266, P29405
[3]   THE ROLE OF NITRIC-OXIDE AND OTHER ENDOTHELIUM-DERIVED VASOACTIVE SUBSTANCES IN VASCULAR-DISEASE [J].
COHEN, RA .
PROGRESS IN CARDIOVASCULAR DISEASES, 1995, 38 (02) :105-128
[4]   SENSITIVITY OF THE ESSENTIAL ZINC-THIOLATE MOIETY OF YEAST ALCOHOL-DEHYDROGENASE TO HYPOCHLORITE AND PEROXYNITRITE [J].
CROW, JP ;
BECKMAN, JS ;
MCCORD, JM .
BIOCHEMISTRY, 1995, 34 (11) :3544-3552
[5]   PREPARATIVE HPLC PURIFICATION OF PROSTAGLANDIN ENDOPEROXIDES AND ISOLATION OF NOVEL CYCLOOXYGENASE-DERIVED ARACHIDONIC-ACID METABOLITES [J].
HECKER, M ;
HATZELMANN, A ;
ULLRICH, V .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (06) :851-855
[6]  
JAESCHKE H, 1995, P SOC EXP BIOL MED, V209, P104
[7]  
KULMACZ RJ, 1985, J BIOL CHEM, V260, P2572
[8]   PHARMACOLOGY OF THE ENDOTHELIUM IN ISCHEMIA-REPERFUSION AND CIRCULATORY SHOCK [J].
LEFER, AM ;
LEFER, DJ .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1993, 33 :71-90
[9]   MODULATION OF LEUKOCYTE-MEDIATED MYOCARDIAL REPERFUSION INJURY [J].
LUCCHESI, BR .
ANNUAL REVIEW OF PHYSIOLOGY, 1990, 52 :561-576
[10]   TUMOR-NECROSIS-FACTOR ENHANCES LOW-DENSITY-LIPOPROTEIN OXIDATIVE MODIFICATION BY MONOCYTES AND ENDOTHELIAL-CELLS [J].
MAZIERE, C ;
AUCLAIR, M ;
MAZIERE, JC .
FEBS LETTERS, 1994, 338 (01) :43-46