Advanced SearchSearch Tips
NAD(P)H-quinone oxidoreductase-1 silencing modulates cytoprotection related protein expression in cisplatin cytotoxicity
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
NAD(P)H-quinone oxidoreductase-1 silencing modulates cytoprotection related protein expression in cisplatin cytotoxicity
Park, Se Ra; Jung, Ju Young; Kim, Young-Jung; Jung, Da Young; Lee, Mee Young; Ryu, Si Yun;
  PDF(new window)
NAD(P)H-quinone oxidoreductase-1 (NQO1) is a down-stream target gene of nuclear factor erythroid 2-related factor 2 (Nrf2), and performs diverse biological functions. Recently, NQO1 is recognized as an effective gene for the cytotoxic inserts with its diverse biological functions, which is focused on antioxidant properties. The aim of present study was to assess the impact of NQO1 knockdown on cytoprotection-related protein expression in cisplatin cytotoxicity by using small interfering (si) RNA targeted on NQO1 gene. Cytotoxicity of cisplatin on ACHN cells was assessed in a dose- and time-dependent manner after siScramble or siNQO1 treatment. After cisplatin treatment, cells were subjected to cell viability assay, western-blot analysis, and immunofluorescence study. The cell viability was decreased in the siNQO1 cells (50%) than the siScramble cells (70%) after 24 h of cisplatin () treatment. Moreover, cytoprotection-related protein expressions were markedly suppressed in the siNQO1 cells after cisplatin treatment. The expression of Nrf2 and Klotho were decreased by 20% and 40%, respectively, of that in siScramble cells. Nrf2 and Klotho activation were also decreased in cisplatin treated siNQO1 cells, confirmed by cytoplasm-tonuclear translocation. Our findings demonstrate that the increased cisplatin-induced cytotoxicity was accompanied by suppressed Nrf2 activation and Klotho expression in siNQO1 cells.
NAD(P)H-quinone oxidoreductase-1;cisplatin;cytotoxicity;nuclear factor erythroid 2-related factor 2;
 Cited by
Aleksunes LM, Reisman SA, Yeager RL, Goedken MJ, Klaassen CD. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice. J Pharmcol Exp Ther 2010, 333, 140-151. crossref(new window)

Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A. Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology 2005, 212, 116-123. crossref(new window)

Bryan HK, Olayanju A, Goldring CE, Park BK. The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol 2013, 85, 705-717. crossref(new window)

Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Perez JM. Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 2007, 7, 3-18. crossref(new window)

Ghattas MH, Chuang LT, Kappas A, Abraham NG. Protective effect of HO-1 against oxidative stress in human hepatoma cell line (HepG2) is independent of telomerase enzyme activity. Int J Biochem Cell Biol 2002, 34, 1619-1628. crossref(new window)

Hu MC, Kuro-o M, Moe OW. Secreted klotho and chronic kidney disease. In: Kuro-o M (ed.). Endocrine FGFs and Klothos. pp. 126-157, Landes Biosciences/Springer Science+Business Media, Austin/New York, 2012.

Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 2010, 24, 3438-3450. crossref(new window)

Hu X, Roberts JR, Apopa PL, Kan YW, Ma Q. Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in Nrf2 null mice. Mol Cell Biol 2006, 26, 940-954. crossref(new window)

Ikushima M, Rakugi H, Ishikawa K, Maekawa Y, Yamamoto K, Ohta J, Chihara Y, Kida I, Ogihara T. Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun 2006, 339, 827-832. crossref(new window)

Jodar L, Mercken EM, Ariza J, Younts C, Gonzalez-Reyes JA, Alcain FJ, Buron I, de Cabo R, Villalba JM. Genetic deletion of Nrf2 promotes immortalization and decreases life span of murine embryonic fibroblasts. J Gerontol A Biol Sci Med Sci 2011, 66, 247-256.

Kim TW, Song IB, Lee HK, Lim JH, Cho ES, Son HY, Park SJ, Kim JW, Yun HI. Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates cisplatin-induced nephrotoxicity in mice. Food Chem Toxicol 2012, 50, 4254-4259. crossref(new window)

Kim YJ, Kim TW, Park SR, Kim HT, Jung DY, Ryu SY, Jung JY. Deletion of NAD(P) H:quinone oxidoreductase 1 represses Mre11-Rad50-Nbs1 complex protein expression in cisplatin-induced nephrotoxicity. Toxicol Lett 2016, 243, 22-30. crossref(new window)

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997, 390, 45-51. crossref(new window)

Leonard MO, Kieran NE, Howell K, Burne MJ, Varadarajan R, Dhakshinamoorthy S, Porter AG, O'Farrelly C, Rabb H, Taylor CT. Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury. FASEB J 2006, 20, 2624-2626. crossref(new window)

Lin L, Zheng J, Zhu W, Jia N. Nephroprotective effect of gelsemine against cisplatin-induced toxicity is mediated via attenuation of oxidative stress. Cell Biochem Biophys 2015, 71, 535-541. crossref(new window)

Lin X, Yang H, Zhou L, Guo Z. Nrf2-dependent induction of NQO1 in mouse aortic endothelial cells overexpressing catalase. Free Radic Biol Med 2011, 51, 97-106. crossref(new window)

Ma Q. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol 2013, 53, 401-426. crossref(new window)

Martins NM, Santos NAG, Curti C, Bianchi MLP, Santos AC. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol 2008, 28, 337-344. crossref(new window)

Masuda H, Chikuda H, Suga T, Kawaguchi H, Kuro-o M. Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice. Mech Ageing Dev 2005, 126, 1274-1283. crossref(new window)

Mitobe M, Yoshida T, Sugiura H, Shirota S, Tsuchiya K, Nihei H. Oxidative stress decreases klotho expression in a mouse kidney cell line. Nephron Exp Nephrol 2005, 101, e67-e74. crossref(new window)

Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009, 284, 13291-13295. crossref(new window)

Nioi P, McMahon M, Itoh K, Yamamoto M, Hayes JD. Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence. Biochem J 2003, 374, 337-348. crossref(new window)

Park JS, Jung JS, Jeong YH, Hyun JW, Le TKV, Kim DH, Choi EC, Kim HS. Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: critical role of hemeoxygenase-1 and NQO1 expression. J Neurochem 2011, 119, 909-919. crossref(new window)

Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997, 389, 300-305. crossref(new window)

Ma Q, Kinneer K, Bi Y, Chan JY, Kan YW. Induction of murine NAD(P)H:quinone oxidoreductase by 2,3,7,8-tetrachlorodibenzo-p-dioxin requires the CNC (cap 'n' collar) basic leucine zipper transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2): cross-interaction between AhR (aryl hydrocarbon receptor) and Nrf2 signal transduction. Biochem J 2004, 377, 205-213. crossref(new window)

Siegel D, Bolton EM, Burr JA, Liebler DC, Ross D. The reduction of ${\alpha}$-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of ${\alpha}$-tocopherolhydroquinone as a cellular antioxidant. Mol Pharmacol 1997, 52, 300-305. crossref(new window)

Siegel D, Gustafson DL, Dehn DL, Han JY, Boonchoong P, Berliner LJ, Ross D. NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol 2004, 65, 1238-1247. crossref(new window)

Sugiura H, Yoshida T, Shiohira S, Kohei J, Mitobe M, Kurosu H, Kuro-o M, Nitta K, Tsuchiya K. Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis. Am J Physiol-Renal Physiol 2012, 302, F1252-F1264. crossref(new window)

Yeligar SM, Machida K, Kalra VK. Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1${\alpha}$ and Nrf2 to attenuate inflammatory cytokine expression. J Biol Chem 2010, 285, 35359-35373. crossref(new window)

Yi YW, Bae I. Effects of solvents on in vitro potencies of platinum compounds. DNA Repair (Amst) 2011, 10, 1084-1085.

Zhu H, Jia Z, Mahaney JE, Ross D, Misra HP, Trush MA, Li Y. The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. Cardiovasc Toxicol 2007, 7, 202-211. crossref(new window)