Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.
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一氧化氮、超氧化物和过氧亚硝酸盐：好的、坏的和丑陋的。
DOI：
10.1152/ajpcell.1996.271.5.c1424
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Koppenol,WH
中科院分区：
文献类型：
--
作者：
Beckman,JS;Koppenol,WH
一氧化氮与大多数细胞间信使相反，因为它通过大多数组织快速且各向同性地扩散，几乎没有反应，但由于氧合血红蛋白的快速破坏而不能通过脉管系统运输。一氧化氮在细胞之间的快速扩散使其能够局部整合血管对湍流的反应，调节神经元的突触可塑性，并控制神经元网络的振荡行为。一氧化氮不一定是短寿命的，本质上并不比氧气更活泼。一氧化氮本身的反应性在体外被大大高估，因为没有提供排出物来去除一氧化氮。一氧化氮在溶液中以微摩尔浓度存在几分钟，然后与氧气反应形成更强的氧化剂，如二氧化氮。一氧化氮在体内几秒钟内通过扩散超过100微米进入红细胞并与氧合血红蛋白反应而被清除。一氧化氮的直接毒性是适度的，但通过与超氧化物反应形成过氧亚硝酸盐（ONOO-）而大大增强。一氧化氮是唯一的生物分子产生足够高的浓度超过超氧化物歧化酶的超氧化物。过亚硝酸盐与大多数生物分子反应相对缓慢，使过亚硝酸盐成为选择性氧化剂。过氧亚硝酸盐修饰蛋白质中的酪氨酸以产生硝基酪氨酸，留下可在体内检测的足迹。硝化结构蛋白，包括神经丝和肌动蛋白，可以破坏丝组装与主要的病理后果。硝基酪氨酸抗体揭示了人体动脉粥样硬化、心肌缺血、脓毒症和肺损伤、炎症性肠病和肌萎缩侧索硬化中的硝化作用。
Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.