Oxidative and nitrative modifications of α-enolase in cardiac proteins from diabetic rats

Oxidative and nitrative modifications of α-enolase in cardiac proteins from diabetic rats
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DOI:
10.1016/j.freeradbiomed.2010.01.010
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发表时间:
2010-04-01
影响因子:
7.4
通讯作者:
Gao, Zhonghong
Gao, Zhonghong
中科院分区:
医学1区
文献类型:
--
作者:
Lu, Naihao;Zhang, Yan;Gao, Zhonghong

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Many studies have reported that oxidative and nitrative stress might be important in the pathogenesis of diabetes. By means of immunoprecipitation analysis, alpha-enolase (EC 4.2.1.11, 2-phospho-D-glycerate hydrolyase) was identified as the important target for oxidative and nitrative modifications in diabetic cardiac proteins. The levels of protein carbonyls and 3-nitrotyrosine residues in alpha-enolase (biomarkers of oxidative and nitrative damage, respectively) from cardiac proteins of diabetic rats were determined and compared with age-matched controls. After 6 weeks of streptozotocin administration, the cardiac proteins from diabetic rats showed: (a) the levels of alpha-enolase expression and nitration were clearly increased, whereas (b) the enolase activity and oxidation status were not significantly changed. By means of immunoprecipitation and liquid chromatography-tandem mass spectrometry analysis, it was found that Tyr 257 and Tyr 131 of alpha-enolase were the most susceptible to nitration in diabetic rat heart. Further studies in vitro revealed a significant contribution of protein tyrosine nitration to the inactivation of enolase. These results suggest that tyrosine nitration of alpha-enolase could contribute to an impaired glycolytic activity in diabetic cardiomyopathy. Meanwhile, the up-regulation of alpha-enolase expression could be a protective mechanism to neutralize oxidative and nitrative stress in diabetes. (C) 2010 Elsevier Inc. All rights reserved.