Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis

被引:366
作者
Landino, LM
Crews, BC
Timmons, MD
Morrow, JD
Marnett, LJ
机构
[1] VANDERBILT UNIV, SCH MED,VANDERBILT CANC CTR,DEPT BIOCHEM, CTR MOL TOXICOL, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, SCH MED,VANDERBILT CANC CTR,DEPT MED, CTR MOL TOXICOL, NASHVILLE, TN 37232 USA
关键词
D O I
10.1073/pnas.93.26.15069
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Peroxynitrite activates the cyclooxygenase activities of constitutive and inducible prostaglandin endoperoxide synthases by serving as a substrate for the enzymes' peroxidase activities. Activation of purified enzyme is induced by direct addition of peroxynitrite or by in situ generation of peroxynitrite from NO coupling to superoxide anion. Cu,Zn-superoxide dismutase completely inhibits cyclooxygenase activation in systems where peroxynitrite is generated in situ from superoxide, In the murine macrophage cell line RAW264.7, the lipophilic superoxide dismutase-mimetic agents, Cu(II) (3,5-diisopropylsalicylic acid)(2), and Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin dose-dependently decrease the synthesis of prostaglandins without affecting the levels of NO synthase or prostaglandin endoperoxide synthase or by inhibiting the release of arachidonic acid, These findings support the hypothesis that peroxynitrite is an important modulator of cyclooxygenase activity in inflammatory cells and establish that superoxide anion serves as a biochemical link between NO and prostaglandin biosynthesis.
引用
收藏
页码:15069 / 15074
页数:6
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