Characterization of endonuclease G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy
Characterization of endonuclease G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy
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心脏肥大过程中核酸内切酶 G 和线粒体肌浆网相关蛋白的表征
DOI：
10.1691/ph.2015.5559
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发表时间：
2015-09-01
期刊：
影响因子：
1.6
通讯作者：
Zhao, Qingwei
中科院分区：
文献类型：
--
作者：
Liang, Xingguang;Ma, Kuifen;Zhao, Qingwei
核酸内切酶G(Endo G)是一种新的心肌肥厚的决定因素。在这里，我们报道了Endo G和线粒体-肌浆网相关蛋白在心肌肥厚过程中的特征，并假设Endo G在心肌肥厚过程中部分通过Mfn2和JP2调节线粒体的功能。我们的结果表明，在苯肾上腺素诱导的心肌肥厚开始时，Endo G水平逐渐升高，并伴随着线粒体膜电位的异常。心肌肥厚早期Mfn2、JP2和Endo G表达上调，而PGC1α直到心肌肥厚后期才表达上调。用siRNA取消Endo G导致线粒体电子传输链与ATP产生的解偶联，并降低PGC1α的表达，这可能是通过影响线粒体和肌浆网的并列通过Mfn2和JP2实现的。此外，取消JP2改变了Endo G的表达并导致线粒体功能障碍，提示心肌肥厚中线粒体的异常很可能是由Endo G引起的。综上所述，我们的研究部分通过Endo G对Mfn2和JP2的影响，建立了Endo G与心肌肥厚时线粒体功能之间的联系，并揭示了Endo G在Mfn2和JP2控制的不良适应性心肌肥厚过程之间的相互作用。
Endonuclease G (Endo G) is a novel determinant of cardiac hypertrophy. Here, we report the characterization of Endo G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy, and hypothesize that Endo G regulate mitochondria] function partly through Mfn2 and Jp2 during cardiac hypertrophy. Our results show that Endo G levels gradually increased at the beginning of phenylephrine-induced cardiac hypertrophy, accompanied by an abnormal mitochondrial membrane potential. The up-regulation of Mfn2, Jp2, and Endo G appeared at an early stage of cardiac hypertrophy, whereas PGC1 alpha was not up-regulated until a later stage. Abolishing Endo G with siRNA led to the uncoupling of the mitochondrial electron transport chain from ATP production and decreased PGC1 alpha expression, likely by affecting the juxtaposition of the mitochondria and the sarcoplasmic reticulunn via Mfn2 and Jp2. Furthermore, abolishing Jp2 altered the expression of Endo G expression and induced mitochondrial dysfunction, suggesting that mitochondrial abnormalities in cardiac hypertrophy are most likely caused by Endo G. Taken together, our study established a link between Endo G and mitochondrial function during cardiac hypertrophy, partly through the effects of Endo G on Mfn2 and Jp2, and revealed a role for Endo G in the crosstalk between the processes controlled by Mfn2 and Jp2 in maladaptive cardiac hypertrophy.