异柠檬酸脱氢酶2（IDH2）的下调加剧了血红素加氧酶（HO）介导的细胞死亡和肥大。
Downregulation of IDH2 exacerbates HO-mediated cell death and hypertrophy.
作者信息
Ku Hyeong Jun, Park Jeen-Woo
机构信息
a School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group , Kyungpook National University , Taegu , Korea.
出版信息
Redox Rep. 2017 Jan;22(1):35-41. doi: 10.1080/13510002.2015.1135581. Epub 2016 Feb 15.
OBJECTIVES
Reactive oxygen species-mediated cell death contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. We recently showed that mitochondrial NADP-dependent isocitrate dehydrogenase (IDH2) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems.
METHODS
In the present study, we demonstrated that HO-induced apoptosis and hypertrophy of H9c2 cardiomyoblasts was markedly exacerbated by small interfering RNA (siRNA) specific for IDH2.
RESULTS
Attenuated IDH2 expression resulted in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. MitoTEMPO, a mitochondria-targeted antioxidant, efficiently suppressed increased caspase-3 activity, increased cell size, and depletion of cellular GSH levels in IDH2 siRNA-transfected cells that were treated with HO.
DISCUSSION
These results indicated that the disruption of cellular redox balance might be responsible for the enhanced HO-induced apoptosis and hypertrophy of cultured cardiomyocytes by the attenuated IDH2 expression.
目的
活性氧介导的细胞死亡参与心血管疾病和心肌功能障碍的病理生理过程。我们最近发现，线粒体烟酰胺腺嘌呤二核苷酸磷酸（NADP）依赖性异柠檬酸脱氢酶2（IDH2）通过为抗氧化系统提供还原型辅酶II（NADPH）发挥抗氧化和抗凋亡蛋白的作用。
方法
在本研究中，我们证明，IDH2特异性小干扰RNA（siRNA）显著加剧了过氧化氢（HO）诱导的H9c2心肌成纤维细胞凋亡和肥大。
结果
IDH2表达减弱导致细胞和线粒体氧化还原状态、线粒体功能以及细胞氧化损伤的改变。线粒体靶向抗氧化剂MitoTEMPO有效抑制了HO处理的IDH2 siRNA转染细胞中半胱天冬酶-3活性增加、细胞大小增加以及细胞内谷胱甘肽（GSH）水平降低。
讨论
这些结果表明，细胞氧化还原平衡的破坏可能是IDH2表达减弱导致HO诱导的培养心肌细胞凋亡和肥大增强的原因。
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