イツミ　モモエ   逸見　百江    所属   川崎医科大学  医学部 一般教養　自然科学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP(+)/NADPH ratio.
掲載誌名	正式名：Cell death and differentiation 略　 称：Cell Death Differ ISSNコード：14765403/13509047
掲載区分	国外
巻・号・頁	22(11),pp.1837-45
著者・共著者	M Itsumi, S Inoue, A J Elia, K Murakami, M Sasaki, E F Lind, D Brenner, I S Harris, I I C Chio, S Afzal, R A Cairns, D W Cescon, A R Elford, J Ye, P A Lang, W Y Li, A Wakeham, G S Duncan, J Haight, A You-Ten, B Snow, K Yamamoto, P S Ohashi, T W Mak
発行年月	2015/11
概要	Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in cells by treatment with lipopolysaccharide (LPS) in vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo. Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP(+)/NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP(+)/NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock.
DOI	10.1038/cdd.2015.38
PMID	25882048