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

Involvement of oxidative modification of proteins related to ATP synthesis in the left ventricles of hamsters with cardiomyopathy.
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与心肌病的仓鼠的左心室相关的蛋白质氧化修饰的参与。

DOI:
10.1038/s41598-017-08546-1
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发表时间:
2017-08-23
期刊:
影响因子:
4.6
通讯作者:
Oikawa S
Oikawa S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ichihara S;Suzuki Y;Chang J;Kuzuya K;Inoue C;Kitamura Y;Oikawa S

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由活性氧积累而增强的炎症在心血管疾病的进展中起重要作用。采用二维氧印迹分析和二维差分凝胶电泳(2D-DIGE)技术,比较了6周龄扩张型心肌病(TO-2)和肥厚型心肌病(Bio14.6)仓鼠与对照仓鼠(F1 B)左心室心肌蛋白的ROS诱导羰基修饰水平。然后,2D电泳结合MALDI-TOF/TOF串联质谱检测心肌病仓鼠与对照仓鼠相比羰基水平升高的18个蛋白质。在两种类型心肌病仓鼠心脏中观察到与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,左心室羰基生成与琥珀酰辅酶A:3-酮酸辅酶A转移酶1活性(r2 = 0.60,P = 0.0007)和ATP浓度(r2 = 0.29,P = 0.037)呈负相关,提示蛋白质羰基化对这些生物分子的水平有负面影响。羰基生成与血浆肌钙蛋白T水平呈显著正相关(r2 = 0.33,P = 0.026).氧化损伤导致的能量代谢减少可能是心肌病左心室损害的原因。
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 2 = 0.60, P = 0.0007) and ATP concentration (r 2 = 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 2 = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.
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