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IDH2 deficiency exacerbates cisplatin nephrotoxicity

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Author(s)
Jee In KimMin Jung KongKwon Moo Park
Keimyung Author(s)
Kim, Jee In
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Free Radical Biology and Medicine
Issued Date
2018
Volume
120
Issue
suppl.1
Abstract
Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) is a major producer of NADPH in the mitochondria and plays a critical role in the redox balance. Cisplatin is an effective anticancer drug, however, its nephrotoxicity, by the breaking of redox balance, limits its use. Here, we investigated whether the cisplatin nephrotoxicity is associated with IDH2. IDH2 gene-deleted (IDH2-/-) and wild type (IDH2+/+) mice were administrated cisplatin with or without Mito-TEMPO, a mitochondria-specific antioxidant. Cisplatin reduced IDH2 activity and expression and NADPH levels in the kidney together with mitochondrial oxidative injury. Mitochondrial damage after cisplatin injection was greater in the IDH2-/-than IDH2+/+ kidneys. These changes were more pronounced in the IDH2-/- than IDH2+/+ kidneys, showing greater renal functional and morphological impairments in the IDH2-/-mouse. Mito-TEMPO reduced those cisplatin-induced kidney injuries both in IDH2-/- and IDH2+/+ mouse. This reduction in the IDH2-/- mouse was more prominent than that in the IDH2+/+ mouse. These results indicate that IDH2 deficiency worsens cisplatin nephrotoxicity by increasing oxidative stress, suggesting that cisplatin-induced nephrotoxicity is associated with mitochondrial IDH2.
Keimyung Author(s)(Kor)
김지인
Publisher
School of Medicine (의과대학)
Citation
Jee In Kim et al. (2018). IDH2 deficiency exacerbates cisplatin nephrotoxicity. Free Radical Biology and Medicine, 120(suppl.1), S75–S75. doi: 10.1016/j.freeradbiomed.2018.04.248
Type
Article
ISSN
0891-5849
Source
https://www.sciencedirect.com/science/article/pii/S0891584918304131
DOI
10.1016/j.freeradbiomed.2018.04.248
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41284
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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