Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors
Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors
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DOI：
10.1016/s0006-291x(02)00602-2
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发表时间：
2002-06-28
影响因子：
3.1
通讯作者：
Song, W
中科院分区：
文献类型：
--
作者：
Lawler, JM;Song, W
一氧化氮（（NO）-N-.）其副产物调节骨骼肌的许多生理功能，包括血流、代谢、葡萄糖摄取和收缩功能。然而，越来越多的证据表明，一氧化氮的过度产生导致许多病理学中的肌肉萎缩，包括慢性心力衰竭、败血症、COPD、肌肉萎缩症和极度废用。有限的数据表明，活性氮物质（RNS），包括（NO）-N-抑制各种酶的潜力。及其下游产物如过氧亚硝酸盐，主要在纯化系统中。我们假设骨骼肌暴露于RNS供体会降低或下调关键抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPX）的活性。从4月龄Fischer-344大鼠中提取膈肌纤维束，并在一系列实验中暴露于（a）0（对照）、1或5 mM二乙胺NONOate（DEANO：（NO）-N-。供体）;（B）0、100、500 μ M或1 mM硝普钠（SNP：（NO）-N-。供体）;（c）0或2 mM S-亚硝基-乙酰青霉胺（SNAP：（NO）-N-.捐助者）;（d）0或500 μ M SIN-1（过氧亚硝酸根供体）作用60分钟。DEANO可使CAT、GPX降低50%，并呈剂量依赖性地抑制Cu，Zn-SOD。SNP可显著降低总SOD、Mn-SOD同工酶、Cu，Zn-SOD同工酶、CAT和GPX的活性，并呈剂量依赖性。两毫摩尔SNAP和500 μ M SIN-1也导致了一个大的和显着的抑制总SOD和CAT。这些数据表明，活性氮物种损害抗氧化酶的功能，在RNS供体特异性和剂量依赖性的方式，并与过量的RNS生产有助于骨骼肌氧化应激和肌肉功能障碍的假设是一致的。(C)2002年爱思唯尔科学（美国）。All rights reserved.
Nitric oxide ((NO)-N-.) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (NO)-N-. and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: (NO)-N-. donor); (b) 0, 100, 500muM, or I mM sodium nitroprusside (SNP: (NO)-N-. donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: (NO)-N-. donor); or (d) 0 or 500muM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 muM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction. (C) 2002 Elsevier Science (USA). All rights reserved.