APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE
APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE
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DOI：
10.1073/pnas.87.4.1620
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发表时间：
1990-02-01
影响因子：
11.1
通讯作者：
FREEMAN, BA
中科院分区：
文献类型：
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作者：
BECKMAN, JS;BECKMAN, TW;FREEMAN, BA
超氧化物歧化酶在许多疾病过程中减少损伤，涉及超氧阴离子自由基（O2-）。作为体内的有毒物质。超氧化物的一个关键目标可能是一氧化氮（NO）。由内皮细胞、巨噬细胞、嗜中性粒细胞和脑突触体产生。已知超氧化物和NO.快速反应形成稳定的过氧亚硝酸根阴离子（ONOO-）。我们已经证明过亚硝酸根的pKa为7.49 ±。0.06在37度。在pH 7.4下质子化后迅速分解，半衰期为1.9秒。过氧亚硝酸盐分解产生强氧化剂，其反应性类似于羟基自由基，如通过脱氧核糖或二甲基亚砜的氧化所评估的。指示羟基自由基的产物产率为5.1 ±。0.1%和24.3 ±。1.0%的添加的过氧亚硝酸盐。产物形成不受金属螯合剂二乙基三胺五乙酸的影响，这表明铁不需要催化氧化。与此相反，去铁胺是一种有效的，竞争性的过氧亚硝酸盐引发的氧化抑制剂，因为去铁胺和过氧亚硝酸盐之间的直接反应，而不是通过铁螯合。我们认为超氧化物歧化酶可能通过阻止过氧亚硝酸盐的形成而保护病理条件下被刺激产生超氧化物和NO的血管组织。
Superoxide dismutase reduces injury in many disease processes, implicating superoxide anion radical (O2-.) as a toxic species in vivo. A critical target of superoxide may be nitric oxide (NO.) produced by endothelium, macrophages, neutrophils, and brain synaptosomes. Superoxide and NO. are known to rapidly react to form the stable peroxynitrite anion (ONOO-). We have shown that peroxynitrite has a pKa of 7.49 .+-. 0.06 at 37.degree. C and rapidly decomposes once protonated with a half-life of 1.9 sec at pH 7.4. Peroxynitrite decomposition generates a strong oxidant with reactivity similar to hydroxyl radical, as assessed by the oxidation of deoxyribose or dimethyl sulfoxide. Product yields indicative of hydroxyl radical were 5.1 .+-. 0.1% and 24.3 .+-. 1.0%, respectively, of added peroxynitrite. Product formation was not affected by the metal chelator diethyltriaminepentaacetic acid, suggesting that iron was not required to catalyze oxidation. In contrast, desferrioxamine was a potent, competitive inhibitor of peroxynitrite-initiated oxidation because of a direct reaction between desferrioxamine and peroxynitrite rather than by iron chelation. We propose that superoxide dismutase may protect vascular tissue stimulated to produce superoxide and NO. under pathological conditions by preventing the formation of peroxynitrite.