Cytochrome c:: a catalyst and target of nitrite-hydrogen peroxide-dependent protein nitration
Cytochrome c:: a catalyst and target of nitrite-hydrogen peroxide-dependent protein nitration
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DOI：
10.1016/j.abb.2003.08.033
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Freeman, BA
中科院分区：
文献类型：
--
作者：
Castro, L;Eiserich, JP;Freeman, BA
蛋白质酪氨酸残基硝化为3-硝基酪氨酸(NO(2)Tyr)既是一氧化氮((NO)-N-)与过氧亚硝酸根(ONOO-)和白细胞过氧化物酶衍生的二氧化氮((NO2)-N-)致病反应的标志和中介。是体内硝化反应的近端介体。细胞色素c是一种呼吸和凋亡信号转导蛋白，定位于线粒体内膜。本文报道了细胞色素c作为亚硝酸盐(NO2-)和过氧化氢(H_2O_2)介导的硝化反应催化剂的一种新功能。细胞色素c通过酪氨酸基和(NO2)-N-的血红素依赖机制催化自身和邻近分子(羟基苯乙酸，锰超氧化物歧化酶)的硝化反应。产生，如吞噬细胞过氧化物酶。虽然细胞色素c和细胞色素c微过氧化物酶-11(mpx-11)的蛋白水解物的低分子量酚硝化产率相似，但当mpx-11作为催化剂时，蛋白质的硝化程度更高。细胞色素c的部分蛋白分解增加了细胞色素c的过氧化物酶活性和硝化活性。当细胞色素c或mpx-11在H_2O_2和NO_2-存在下暴露于细胞色素C或mpx-11时，锰超氧化物歧化酶发生广泛的酪氨酸硝化，催化活性没有明显下降。这些结果揭示了翻译后酪氨酸修饰的机制，该机制是由线粒体和胞质中都存在的丰富的血红蛋白介导的。数据还推断，能够作为有效的硝化催化剂的特定蛋白质的分布可以为生物分子硝化反应提供空间和分子上的特异性。(C)2003 Elsevier Inc.保留所有权利。
Nitration of protein tyrosine residues to 3-nitrotyrosine (NO(2)Tyr) serves as both a marker and mediator of pathogenic reactions of nitric oxide ((NO)-N-.), with peroxynitrite (ONOO-) and leukocyte peroxidase-derived nitrogen dioxide ((NO2)-N-.) being proximal mediators of nitration reactions in vivo. Cytochrome c is a respiratory and apoptotic signaling heme protein localized exofacially on the inner mitochondrial membrane. We report herein a novel function for cytochrome c as a catalyst for nitrite (NO2-) and hydrogen peroxide (H2O2)-mediated nitration reactions. Cytochrome c catalyzes both self- and adjacent-molecule (hydroxyphenylacetic acid, Mn-superoxide dismutase) nitration via heme-dependent mechanisms involving tyrosyl radical and (NO2)-N-. production, as for phagocyte peroxidases. Although low molecular weight phenolic nitration yields were similar for cytochrome c and the proteolytic fragment of cytochrome c microperoxidase-11 (MPx-11), greater extents of protein nitration occurred when MPx-11 served as catalyst. Partial proteolysis of cytochrome c increased both the peroxidase and nitrating activities of cytochrome c. Extensive tyrosine nitration of Mn-superoxide dismutase occurred when exposed to either cytochrome c or MPx-11 in the presence of H2O2 and NO2-, with no apparent decrease in catalytic activity. These results reveal a post-translational tyrosine modification mechanism that is mediated by an abundant hemoprotein present in both mitochondrial and cytosolic compartments. The data also infer that the distribution of specific proteins capable of serving as potent catalysts of nitration can lend both spatial and molecular specificity to biomolecule nitration reactions. (C) 2003 Elsevier Inc. All rights reserved.