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与 ATP 合成相关的蛋白质氧化修饰在心肌病仓鼠左心室中的作用。

Involvement of oxidative modification of proteins related to ATP synthesis in the left ventricles of hamsters with cardiomyopathy.

机构信息

Graduate School of Regional Innovation Studies, Tsu, Japan.

Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan.

出版信息

Sci Rep. 2017 Aug 23;7(1):9243. doi: 10.1038/s41598-017-08546-1.

Abstract

Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r  = 0.60, P = 0.0007) and ATP concentration (r  = 0.29, P = 0.037), suggesting that protein carbonylation has negative effects on the levels of these biomolecules. Furthermore, carbonyl production significantly correlated with plasma Troponin T level (r  = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.

摘要

活性氧自由基的积累引起的炎症在心血管疾病的进展中起着至关重要的作用。使用 2D-oxyblot 分析和 2D-差异图像凝胶电泳(2D-DIGE),我们比较了扩张型(TO-2)和肥厚型心肌病(Bio14.6)以及对照仓鼠(F1B)的整个左心室中 ROS 诱导的心肌蛋白羰基修饰水平。然后,2D 电泳结合 MALDI-TOF/TOF 串联质谱检测到心肌病仓鼠中 18 种蛋白质的羰基水平升高,与对照仓鼠相比。在两种类型的心肌病仓鼠的心脏中观察到与 ATP 合成相关的蛋白质的羰基修饰,包括柠檬酸循环和电子传递系统。进一步分析表明,左心室羰基产物与琥珀酰辅酶 A:3-酮酸辅酶 A 转移酶 1 活性(r=0.60,P=0.0007)和 ATP 浓度(r=0.29,P=0.037)呈负相关,表明蛋白质羰基化对这些生物分子的水平有负面影响。此外,羰基产物与血浆肌钙蛋白 T 水平显著相关(r=0.33,P=0.026)。氧化损伤导致的能量代谢减少可能导致心肌病左心室损伤的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6242/5569096/60716391469b/41598_2017_8546_Fig1_HTML.jpg

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