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Effect of Antioxidant Enzymes on Hypoxia-Induced HIF-$1{\alpha}$ Accumulation and Erythropoietin Activity  

Cho, Eun-Jin (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Cho, Ki-Woon (Department of Oral Biochemistry, College of Dentistry, Chosun University)
Chung, Kyoung-Jin (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Yang, Hee-Young (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Park, Hyang-Rim (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Park, Byung-Ju (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Lee, Tae-Hoon (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Publication Information
International Journal of Oral Biology / v.34, no.4, 2009 , pp. 205-213 More about this Journal
Abstract
The mechanisms underlying the actions of the antioxidants upon reactive oxygen species (ROS) generation by NADPH oxidase complex have remained uncertain. In this study, we investigated NADPH oxidase activity and the role of antioxidant enzymes upon the generation of ROS during hypoxic stress. ROS generation was found to increase in the mouse kidney under hypoxic stress in a time-dependent manner. Moreover, we found in MCT cells that hypoxia-induced hydrogen peroxide production was decreased by NAC pretreatment. We further analyzed HIF-$1{\alpha}$, PHD2 and VHL expression in the NAC-pretreated MCT cells and assessed the response of antioxidant enzymes at the transcriptional and translational levels. SOD3 and Prdx2 were significantly increased during hypoxia in the mouse kidney. We also confirmed in hypoxic $Prdx2^{-/-}$ and SOD3 transgenic mice that erythropoietin (EPO) is transcriptionally regulated by HIF-$1{\alpha}$. In addition, although EPO protein was found to be expressed in a HIF-$1{\alpha}$ independent manner in three mouse lines, its activity differed markedly between normal and $Prdx2^{-/-}$/SOD3 transgenic mice during hypoxic stress. In conclusion, our current results indicate that NADPH oxidase-mediated ROS generation is associated with hypoxic stress in the mouse kidney and that SOD3 and Prdx2 cooperate to regulate cellular redox reactions during hypoxia.
Keywords
hypoxia; reactive oxygen species; NADPH oxidase; peroxiredoxin 2; superoxide dismutase 3; erythropoietin;
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1 Carlsson LM, Jonsson J, Edlund T, Marklund SL. Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc Natl Acad Sci. 1995;92:6264-68   DOI   ScienceOn
2 Kang SW, Baines IC, Rhee SG. Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. J Biol Chem. 1998;273:6303-11   DOI   ScienceOn
3 Kim HA, Kim SH, Ko HM, Choi JH, Kim KJ, Oh SH, Cho KO, Choi IW, Im SY. Nitric oxide plays a key role in the platelet-activating factor-induced enhancement of resistance against systemic candidiasis. Immunology. 2008;124:428-35   DOI   ScienceOn
4 Moos PJ, Edes K, Cassidy P, Massuda E, Fitzpatrick FA. Electrophilic prostaglandins and lipid aldehydes repress redox-sensitive transcription factors p53 and hypoxiainducible factor by impairing the selenoprotein thioredoxin reductase. J Biol Chem. 2003;278:745-50   DOI   ScienceOn
5 Weidemann A, Johnson RS. Nonrenal regulation of EPO synthesis. Kidney Int. 2009;75:682-8   DOI   ScienceOn
6 Callapina M, Zhou J, Schmid T, K$\ddot{o}$hl R, Br$\ddot{u}$ne, B. NO restores HIF-1$\alpha$ hydroxylation during hypoxia : role of reactive oxygen species. Free Radic Biol Med. 2005;39: 925-36   DOI   ScienceOn
7 Zelko IN, Folz RJ. Extracellular superoxide dismutase functions as a major repressor of hypoxia-induced erythropoietin gene expression. Endocrinology. 2005;146:332-40   DOI   ScienceOn
8 Liu JQ, Zelko IN, Erbynn EM, Sham JS, Folz RJ. Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox). Am J Physiol Lung Cell Mol Physiol. 2006;290:L2-10   DOI   ScienceOn
9 Li X, Kimura H, Hirota K, Sugimoto H, Kimura N, Takahashi N, Fujii H, Yoshida H. Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-gamma in human proximal renal tubular cells. Nephrol Dial Transplant. 2007;22:1041-51   DOI   ScienceOn
10 Higgins DF, Kimura K, Bernhardt WM, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson RS, Kretzler M, Cohen CD, Eckardt KU, Iwano M, Haase VH. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest. 2007;117:3810-20   DOI   ScienceOn
11 Salceda S, Caro J. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem. 1997;272:22642-7   DOI   ScienceOn
12 Martyn KD, Frederick LM, Loehneysen K von, Dinauer MC, Knaus UG. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal. 2006;18:69-82   DOI   ScienceOn
13 Stockmann C, Fandrey J. Hypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression. Clin Exp Pharmacol Physiol. 2006;33:968-79   DOI   ScienceOn
14 Huang LE, Gu J, Schau M, Bunn HF. Regulation of hypoxiainducible factor 1a is mediated by an $O_2$   DOI   ScienceOn
15 Nonn L, Berggren M, Powis G. Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis. Mol Cancer Res. 2003;1:682-9   ScienceOn
16 Semenza GL, Agani F, Feldser D, Iyer N, Kotch L, Laughner E, Yu A. Hypoxia, HIF-1, and the pathophysiology of common human diseases. Adv Exp Med Biol. 2000;475:123-30   ScienceOn
17 Block ML. NADPH oxidase as a therapeutic target in Alzheimer's disease. BMC Neurosci. 2008;9:1-8
18 Nangaku M. Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. J Am Soc Nephrol. 2006;17:17-25   DOI
19 Kang SW, Chae HZ, Seo MS, Kim K, Baines IC, Rhee SG. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J Biol Chem. 1998;273:6297-302   DOI   ScienceOn
20 Marklund SL. Expression of extracellular superoxide dismutase by human cell lines. Biochem J. 1990;266:213-9   DOI   ScienceOn
21 Suliman HB, Ali M, Piantadosi CA. Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood. 2004;104:43-50   DOI   ScienceOn
22 Guzy RD, Schumacker PT. Oxygen sensing by mitochondria at complex III: the paradox of increased ROS during hypoxia. Exp Physiol. 2006;91:807-19   DOI   ScienceOn
23 Zuo L, Clanton TL. Reactive oxygen species formation in the transition to hypoxia in skeletal muscle. Am J Physiol Cell Physiol. 2005;289:C207-16   DOI   ScienceOn
24 Jun JH, Lee HL, Baek JH. Stimulatory effect of N-acetylcysteine on odontoblastic differentiation. Int J Oral Biol. 2008;33:187-95   과학기술학회마을   ScienceOn
25 Tajima M, Kurashima Y, Sugiyama K, Ogura T, Sakagami H. The redox state of glutathione regulates the hypoxic induction of HIF-1. Eur J Pharmacol. 2009;606:45-9   DOI   ScienceOn
26 Wood ZA, Schr$\ddot{o}$der E, Robin Harris J, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci. 2003;28:32-40   DOI   ScienceOn
27 Eckardt KU, Rosenberger C, J$\ddot{u}$rgensen JS, Wiesener MS. Role of hypoxia in the pathogenesis of renal disease. Blood Purif. 2003;21:253-57   DOI   PUBMED   ScienceOn
28 Marxsen JH, Stengel P, Doege K, Heikkinen P, Jokilehto T, Wagner T, Jelkmann W, Jaakkola P, Metzen E. Hypoxiainducible factor-1 (HIF-1) promotes its degradation by induction of HIF-$\alpha$-prolyl-4-hydroxylases. Biochem J. 2004;381:761-7   DOI   ScienceOn
29 Lee TH, Kim SU, Yu SL, Kim SH, Park DS, Moon HB, Dho SH, Kwon KS, Kwon HJ, Han YH, Jeong S, Kang SW, Shin HS, Lee KK, Rhee SG, Yu DY. Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood. 2003;101:5033-8   DOI   ScienceOn
30 Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, Hattori M, Sakaki Y, Sumimoto H. A novel superoxideproducing NAD(P)H oxidase in kidney. J Biol Chem. 2001;276:1417-23   DOI   ScienceOn
31 Kim SH, Kim MO, Gao P, Youm CA, Park HR, Lee TS, Kim KS, Suh JG, Lee HT, Park BJ, Ryoo ZY, Lee TH. Overexpression of extracellular superoxide dismutase (EC-SOD) in mouse skin plays a protective role in DMBA/TPA-induced tumor formation. Oncol Res 2005;15:333-41   DOI   ScienceOn
32 Wang J, Biju MP, Wang MH, Haase VH, Dong Z. Cytoprotective effects of hypoxia against cisplatin-induced tubular cell apoptosis: involvement of mitochondrial inhibition and p53 suppression. J Am Soc Nephrol. 2006;17:1875-85   DOI   ScienceOn
33 Zou AP, Li N, Cowley AW Jr. Production and actions of superoxide in the renal medulla hypertension. Hypertension. 2001a;37:547-53   DOI   ScienceOn
34 Zou AP, Yang ZZ, Li PL, Cowley AW Jr. Oxygen-dependent expression of hypoxia-inducible factor-1alpha in renal medullary cells of rats. Physiol Genomics. 2001b;6:159-68   DOI   ScienceOn
35 Basile DP, Donohoe DL, Roethe K, Mattson DL. Chronic renal hypoxia following ischemia/reperfusion injury: effects of L-arginine on hypoxia and secondary damage. Am J Physiol Renal Physiol. 2003;284:F338-48   DOI   ScienceOn
36 Kawahara T, Ritsick D, Cheng G, Lambeth JD. Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. J Biol Chem. 2005;280:31859-69   DOI   ScienceOn
37 Park SH, Chung YM, Lee YS, Kim HJ, Kim JS, Chae HZ, Yoo YD. Antisense of human peroxiredoxin II enhances radiationinduced cell death. Clin Cancer Res. 2000;6:4915-20   ScienceOn
38 Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335-44   DOI   ScienceOn
39 Mittal M. Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature. Circ Res. 2007;101:258-67   DOI   ScienceOn