Alterations of Mitochondrial Enzymes Contribute to Cardiac Hypertrophy before Hypertension Development in Spontaneously Hypertensive Rats
Alterations of Mitochondrial Enzymes Contribute to Cardiac Hypertrophy before Hypertension Development in Spontaneously Hypertensive Rats
复制标题
线粒体酶的改变导致自发性高血压大鼠高血压发生之前的心脏肥大
DOI：
10.1021/pr801059u
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Fang, Ning-Yuan
中科院分区：
文献类型：
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作者：
Meng, Chao;Jin, Xian;Fang, Ning-Yuan
线粒体功能障碍最近被认为与心肌肥厚和高血压的发生密切相关。然而，线粒体在肥大发病机制早期阶段的详细分子事件仍不清楚。应用二维荧光差示凝胶电泳法(2D-DGE)结合MALDI-TOF/TOF串联质谱仪，通过比较自发性高血压大鼠(SHR)和年龄匹配的正常血压Wistar京都(WKY)大鼠，鉴定高血压前期/高血压心肌肥厚大鼠左室心肌线粒体线粒体蛋白的变化。结果显示，在4周龄正常血压的SHR肥厚的左心室中，33个线粒体蛋白点发生明显改变，其中17个下调，16个上调。这种变化比20周大的高血压自发性高血压大得多。在全部变化中，三功能酶α亚单位(HADHA)和NADH脱氢酶1α亚复合体10(Ndufa10)这两种线粒体酶在SHR株中的表达具有特殊的表达修饰模式。这些数据将为研究线粒体功能障碍在心肌肥厚发展中的潜在作用提供新的线索。
Mitochondrial dysfunction is recently thought to be tightly associated with the development of cardiac hypertrophy as well as hypertension. However, the detailed molecular events in mitochondria at early stages of hypertrophic pathogenesis are still unclear. Applying two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, here we identified the changed mitochondrial proteins of left ventricular mitochondria in prehypertensive/hypertensive stages of cardiac hypertrophy through comparing spontaneously hypertensive rats (SHR) and the age-matched normotensive Wistar Kyoto (WKY) rats. The results revealed that in the hypertrophic left ventricle of SHR as early as 4 weeks old with normal blood pressure, 33 mitochondrial protein spots presented significant alterations, with 17 down-regulated and 16 up-regulated. Such alterations were much greater than those in 20-week-old SHR with elevated blood pressure. Of the total alterations, the expression of two mitochondrial enzymes, trifunctional enzyme alpha subunit (Hadha) and NADH dehydrogenase 1 alpha subcomplex 10 (Ndufa 10), were found to have special expression modification patterns in SHR strain. These data would provide new clues to investigate the potential contribution of mitochondrial dysfunction to the development of cardiac hypertrophy.