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Characterization of mitochondrial NADH dehydrogenase 1 alpha subcomplex 10 variants in cardiac muscles from normal Wistar rats and spontaneously hypertensive rats: Implications in the pathogenesis of hypertension

机译:正常Wistar大鼠和自发性高血压大鼠心肌中线粒体NADH脱氢酶1 alpha亚复合物10个变体的表征:对高血压发病机制的影响

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摘要

Mitochondrial dysfunction has been increasingly associated with the development of cardiovascular diseases, including hypertension and cardiac hypertrophy. In the present study, NADH dehydrogenase la subcomplex 10 (Ndufa10) was characterized from the left ventricular muscles of spontaneously hypertensive rats (SHRs) and normal Wistar Kyoto (WKY) rats. Western blot analysis demonstrated that there was a shift in the molecular weight (MW) and in the isoelectric point (pI) of the Ndufa10 protein from SHRs and WKY rats. Mass spectrometric analysis revealed that the replacement of an aspartate residue with asparagine at amino acid position 120 was the biochemical difference between the two Ndufa10 isoforms. Further analysis using the bacterially expressed proteins Ndufa10-120N (WKY) and Ndufa10-120D (SHR) revealed that the shift in the pI and MW of the two Ndufa10 isoforms was solely caused by the amino acid mutation, and not by post-translational modifications. Since deficiencies of the mitochondrial complex I are the most common defects in the oxidative phosphorylation system, further studies are required to study the difference between the activities of the two Ndufa10 variants, and their role in the pathogenesis of hypertension.
机译:线粒体功能障碍与心血管疾病的发展越来越相关,包括高血压和心脏肥大。在本研究中,NADH脱氢酶la亚复合体10(Ndufa10)的特征是自发性高血压大鼠(SHRs)和正常Wistar Kyoto(WKY)大鼠的左心室肌。 Western印迹分析表明,来自SHR和WKY大鼠的Ndufa10蛋白的分子量(MW)和等电点(pI)发生了变化。质谱分析表明,天冬氨酸残基在氨基酸位置120处被天冬氨酸取代是两种Ndufa10亚型之间的生化差异。使用细菌表达的蛋白质Ndufa10-120N(WKY)和Ndufa10-120D(SHR)进行的进一步分析显示,这两种Ndufa10同工型的pI和MW移位仅由氨基酸突变引起,而不是由翻译后修饰引起。由于线粒体复合物I的缺陷是氧化磷酸化系统中最常见的缺陷,因此需要进一步研究以研究两种Ndufa10变体活性之间的差异以及它们在高血压发病机理中的作用。

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