PEROXYNITRITE FORMATION FROM MACROPHAGE-DERIVED NITRIC-OXIDE

被引:1020
作者
ISCHIROPOULOS, H [1 ]
ZHU, L [1 ]
BECKMAN, JS [1 ]
机构
[1] UNIV ALABAMA, DEPT ANESTHESIOL, 619 S 19TH ST, BIRMINGHAM, AL 35294 USA
关键词
D O I
10.1016/0003-9861(92)90433-W
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
Peroxynitrite formation by rat alveolar macrophages activated with phorbol 12-myristate 13-acetate was assayed by the Cu,Zn superoxide dismutase-catalyzed nitration of 4-hydroxyphenylacetate. The inhibitor of nitric oxide synthesis N-methyl-l-arginine prevented the Cu,Zn Superoxide dismutase-catalyzed nitration of 4-hydroxyphenylacetate by stimulated macrophages, while Cu-depleted Zn superoxide dismutase did not catalyze the formation of 3-nitro-4-hydroxyphenylacetate either in vitro or in the presence of activated macrophages. The rate of phenolic nitration by activated macrophages was 9 ± 2 pmol · 106 cells-1 · min-1 (mean ± STD). Only 8% of synthetic peroxynitrite was trapped by superoxide dismutase, which suggested that the rate of peroxynitrite formation may have been as high as 0.11 nmol · 106 cells-1 · min-1. This upper estimate was consistent with N-methyl-l-arginine increasing the amount of superoxide detected with cytochrome c by 0.12 nmol · 106 cells-1 · min-1. The rate of nitrite and nitrate accumulation was 0.10 ± 0.001 nmol · 106 cells-1 · min-1, suggesting that the majority of nitric oxide produced by activated macrophages may have been converted to peroxynitrite. The formation of a relatively long lived, strong oxidant from the reaction of nitric oxide and superoxide in activated macrophages may contribute to inflammatory cell-mediated tissue injury. © 1992.
引用
收藏
页码:446 / 451
页数:6
相关论文
共 46 条
[1]  
ALBINA JE, 1989, J IMMUNOL, V143, P3641
[2]  
BABIOR BM, 1984, BLOOD, V64, P959
[3]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624
[4]   KINETICS OF SUPEROXIDE DISMUTASE-CATALYZED AND IRON-CATALYZED NITRATION OF PHENOLICS BY PEROXYNITRITE [J].
BECKMAN, JS ;
ISCHIROPOULOS, H ;
ZHU, L ;
VANDERWOERD, M ;
SMITH, C ;
CHEN, J ;
HARRISON, J ;
MARTIN, JC ;
TSAI, M .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 298 (02) :438-445
[5]   REPERFUSION ARRHYTHMIAS - DOSE-RELATED PROTECTION BY ANTI-FREE RADICAL INTERVENTIONS [J].
BERNIER, M ;
MANNING, AS ;
HEARSE, DJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (05) :H1344-H1352
[6]   NITRIC-OXIDE MEDIATES GLUTAMATE NEUROTOXICITY IN PRIMARY CORTICAL CULTURES [J].
DAWSON, VL ;
DAWSON, TM ;
LONDON, ED ;
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6368-6371
[7]  
DING AH, 1988, J IMMUNOL, V141, P2407
[8]   PHOTOLYSIS OF THE N=N BOND IN TRIOXODINITRATE - REACTION BETWEEN TRIPLET NO- AND O2 TO FORM PEROXONITRITE [J].
DONALD, CE ;
HUGHES, MN ;
THOMPSON, JM ;
BONNER, FT .
INORGANIC CHEMISTRY, 1986, 25 (16) :2676-2677
[9]   A DUAL ROLE FOR CALCIUM IN REGULATION OF SUPEROXIDE GENERATION BY STIMULATED RAT ALVEOLAR MACROPHAGES [J].
DORIO, RJ ;
NELSON, J ;
FORMAN, HJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1987, 928 (02) :137-143
[10]   MURINE CYTOTOXIC ACTIVATED MACROPHAGES INHIBIT ACONITASE IN TUMOR-CELLS - INHIBITION INVOLVES THE IRON-SULFUR PROSTHETIC GROUP AND IS REVERSIBLE [J].
DRAPIER, JC ;
HIBBS, JB .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (03) :790-797