title: Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.
abstract: Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage.
  quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1(-/-) mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1(-/-) mice, the cellular NADPH/NADP(+) ratio was significantly higher and NOX activity was markedly higher than in those of NQO1(+/+) mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADP(+) ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP(+) modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Gil-Tae
authors.initials: GT
authors.lastname: Gang
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Jung-Ran
authors.initials: JR
authors.lastname: Noh
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Kyoung-Shim
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Nephrology Research Department, Chungnam National University Hospital, Chunggu, Daejeon, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Nephrology Research Department, Chungnam National University Hospital, Chunggu, Daejeon, Republic of Korea.
authors.forename: Dae Eun
authors.initials: DE
authors.lastname: Choi
authors.affiliation: Nephrology Research Department, Chungnam National University Hospital, Chunggu, Daejeon, Republic of Korea.
authors.forename: Kang Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, School of Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Research Center for Endocrine and Metabolic Diseases, School of Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea. Electronic address: chullee@kribb.re.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D020536:Enzyme Activators / Q000494:pharmacology; D015870:Gene Expression; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000235:genetics*; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D020536:Enzyme Activators; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D009249:NADP; C014638:beta-lapachone; D003404:Creatinine; D019255:NADPH Oxidases; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse
keywords: Free radicals; Ischemia/reperfusion injury; NADPH oxidase; NQO1; β-Lapachone