Peroxynitrite-Mediated Oxidative Modifications of Complex II: Relevance in Myocardial Infarction

Title

Peroxynitrite-Mediated Oxidative Modifications of Complex II: Relevance in Myocardial Infarction

Creator

Zhang L W; Chen C L; Kang P T; Garg V; Hu K L; Green-Church K B; Chen Y R

Publisher

Biochemistry

Date

2010
2010-03

Description

Increased O-2(center dot-) and NO production is a key mechanism of mitochondrial dysfunction in mycocardial ischemia/reperfusion injury. In complex impairment and enhanced tyrosine nitration of the 70 kDa FAD-binding protein occur in the post-ischemic myocardium and are thought to be mediated by peroxynitrite (OONO-) ill vivo [Chen, Y.-R., et ill. (2008) J. Biol. Chem. 283, 27991-28003]. To gain deeper insights into the redox protein thiols involved ill OONO--mediated Oxidative post-translational modifications relevant ill myocardial infarction, We subjected Isolated myocardial complex 11 to ill vltro protein nitration with OONO-. This resulted ill site-specific nitration at the 70 kDa polypeptide and impairment of complex II-derived electron transfer activity. Under reducing conditions, the gel band of the 70 kDa POlyPePtldC MIS subjected to in-gel trypsin/chymotrypsin digestion and then LC-MS/MS analysis Nitration Of Y-56 and Y-142 was previosly reported. Further analysis revealed that C-267, C-476 and C-537 are involved ill OONO--mediated S-sulfonation. To identify the disulfide formation mediated by OONO-, nitrated complex 11 was alkylated with iodoacetamide. In-gel proteolytic digestion and LC-MS/MS analysis were conducted under nonreducing conditions. The MS/MS data were examined with MassMatrix, indicating that three cysteine pairs, C-306-C-312,C-439-C-444, and C-288-C-575, were involved in OONO--mediated disulfide formation. Immuno-spin trapping with an anti-DMPO antibody and subsequent MS Was used to define Oxidative modification with protein radical formation. An OONO--dependent DMPO adduct was detected. and further LC-MS/MS analysis indicated C-288 and C-655 were involved in DMPO binding. These I-CSLIltS offered a complete profile of OONO--mediated Oxidative modifications that may be relevant Ill the disease model of myocardial infarction.

Subject

Biochemistry & Molecular Biology; cytochrome-c; fatty-acids; identification; membrane; mitochondrial; modulation; nitric-oxide; postischemic heart; succinate-ubiquinone; thiyl

Identifier

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

2529-2539

Issue

11

Volume

49

Citation

Zhang L W; Chen C L; Kang P T; Garg V; Hu K L; Green-Church K B; Chen Y R, “Peroxynitrite-Mediated Oxidative Modifications of Complex II: Relevance in Myocardial Infarction,” NEOMED Bibliography Database, accessed September 25, 2021, https://neomed.omeka.net/items/show/7653.

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