Upregulation of alpha-enolase protects cardiomyocytes from phenylephrine-induced hypertrophy
Upregulation of alpha-enolase protects cardiomyocytes from phenylephrine-induced hypertrophy
复制标题
α-烯醇化酶的上调可保护心肌细胞免受去氧肾上腺素诱导的肥大的影响
DOI：
10.1139/cjpp-2017-0282
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发表时间：
2018
影响因子：
2.1
通讯作者：
Liu Peiqing
中科院分区：
文献类型：
--
作者：
Gao Si;Liu Xue ping;Wei Li hua;Lu Jing;Liu Peiqing
心脏肥大常指通过多种因素导致的心肌异常生长。心肌细胞肥大的机制已被广泛研究，使用新生大鼠心肌细胞与苯异黄酮处理。α-烯醇化酶是一种糖酵解酶，除催化活性外，还具有“多功能”。其对心功能不全的可能作用仍有待确定。本研究旨在观察α-烯醇化酶在心肌肥厚过程中的变化，探讨其在心肌肥厚病理过程中的作用。我们发现，α-烯醇化酶的mRNA和蛋白水平显着上调，在肥大的大鼠心脏腹主动脉缩窄和苯肾上腺素处理的新生大鼠心肌细胞。此外，在心肌细胞中通过RNA干扰敲低α-烯醇化酶模拟肥大反应并加重苯肾上腺素诱导的肥大，而不降低烯醇化酶的总糖酵解活性。此外，α-烯醇化酶的敲低导致正常和苯肾上腺素处理的心肌细胞中GATA 4表达增加。我们的结果表明，α-烯醇化酶在心肌肥厚时升高是代偿性的。它在保护心肌细胞免受病理性肥大方面发挥催化独立作用。
Cardiac hypertrophy often refers to the abnormal growth of heart muscle through a variety of factors. The mechanisms of cardiomyocyte hypertrophy have been extensively investigated using neonatal rat cardiomyocytes treated with phenylephrine. α-Enolase is a glycolytic enzyme with “multifunctional jobs” beyond its catalytic activity. Its possible contribution to cardiac dysfunction remains to be determined. The present study aimed to investigate the change of α-enolase during cardiac hypertrophy and explore its role in this pathological process. We revealed that mRNA and protein levels of α-enolase were significantly upregulated in hypertrophic rat heart induced by abdominal aortic constriction and in phenylephrine-treated neonatal rat cardiomyocytes. Furthermore, knockdown of α-enolase by RNA interference in cardiomyocytes mimicked the hypertrophic responses and aggravated phenylephrine-induced hypertrophy without reducing the total glycolytic activity of enolase. In addition, knockdown of α-enolase led to an increase of GATA4 expression in the normal and phenylephrine-treated cardiomyocytes. Our results suggest that the elevation of α-enolase during cardiac hypertrophy is compensatory. It exerts a catalytic independent role in protecting cardiomyocytes against pathological hypertrophy.