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Mitochondrial NADP(+)-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury

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Author(s)
Sang Jun HanHee-Seong JangMi Ra NohJinu KimMin Jung KongJee In KimJeen-Woo ParkKwon Moo Park
Keimyung Author(s)
Kim, Jee In
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Journal of American Society of Nephrology
Issued Date
2018
Volume
29
Issue
4
Keyword
Mitochondrial isocitrate dehydrogenaseKidney ischemia reperfusionNADPHReactive oxidative species
Abstract
Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.
Keimyung Author(s)(Kor)
김지인
Publisher
School of Medicine
Citation
Sang Jun Han et al. (2018). Mitochondrial NADP(+)-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury. Journal of American Society of Nephrology, 29(4), 1200–1215. doi: 10.1681/ASN.2016030349
Type
Article
ISSN
1046-6673
DOI
10.1681/ASN.2016030349
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32811
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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