Effects of anti-nitration on thioredoxin activation and postischemic myocardial apoptosisEnglish Full Text

ZHANG Hang-xiang1,2,ZANG Yi-min2,LI Shu-zhuang2,GAO Feng2,MA Xin-liang2 (1.Department of Geriatrics,Xijing Hospital,2.Department of Physiology,Fourth Military Medical University,Xi’an 710032,Shaanxi,China)

Abstract: AIM Thioredoxin（Trx） is an important anti-apoptotic molecule.Several recent studies have demonstrated that Trx activity is decreased by post-translational nitrative modification.The present study was designed to determine whether anti-nitration treatment could restore thioredoxin activity.METHODS: C57/B16 mice were subjected to 30 min of myocardial ischemia and treated with either vehicle or FP-15（peroxynitrite decomposition catalyst,5 mg/kg,ip） 10 min before reperfusion.RESULTS: In cardiac tissues obtained from ischemic/reperfused heart,total NO production and cardiac nitrotyrosine were markedly increased,significant Trx nitration was detected,Trx activity was markedly inhibited,Trx/ASK1（apoptosis signal-regulating kinase-1） complex formation was abolished,and ASK-1 activity was increased.Treatment with FP-15 10 min before reperfusion blocked nitrotyrosine production [（1.88±0.23） nmol/g protein vs（0.29±0.14） nmol/g protein,P＜0.01],reduced Trx nitration（51.9±5.1 vs 18.2±2.9,P＜0.01）,restored Trx activity [（0.98±0.11） mol/（min·g protein） vs（1.68±0.12） mol/（min·g protein）,P＜0.01],decreased P38 MAPK activity（1.48±0.04 vs 0.59±0.10,P＜0.01）,attenuated caspase 3 activation [（18.0±0.9） μmol/（h·g protein） vs（7.7±1.6） μmol/（h·g protein）,P＜0.01] and reduced infarct size（39.7%±2.8% vs 23.7%±2.3%,P＜0.01）.CONCLUSION: Anti-nitration treatment can restore thioredoxin activity and improve the myocardial ischemia/reperfusion outcome.

Keywords：

apoptosis; thioredoxin; protein nitration; ischemia/reperfusion;

DOI：
10.13191/j.chj.2008.03.11.zhanghx.005
Series：
Subject：
Classification Code：
R541

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Effects of anti-nitration on thioredoxin activation and postischemic myocardial apoptosisEnglish Full Text

ZHANG Hang-xiang1,2,ZANG Yi-min2,LI Shu-zhuang2,GAO Feng2,MA Xin-liang2 (1.Department of Geriatrics,Xijing Hospital,2.Department of Physiology,Fourth Military Medical University,Xi’an 710032,Shaanxi,China)

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