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Blood, 1 July 2004, Vol. 104, No. 1, pp. 43-50. Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2003-07-2240. This Article Full Text (PDF) All Versions of this Article: 2003-07-2240v1 104/1/43    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Suliman, H. B Articles by Piantadosi, C. A Search for Related Content PubMed PubMed Citation Articles by Suliman, H. B Articles by Piantadosi, C. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 9, 2003 Accepted February 13, 2004 Superoxide Dismutase-3 Promotes Full Expression of the Erythropoietin Response to Hypoxia Hagir B Suliman, Mervat Ali, and Claude A Piantadosi* Medicine, Duke University, Durham, NC, USA; Anesthesiology, Duke University, Durham, NC, USA Anesthesiology, Duke University, Durham, NC, USA * Corresponding author; email: piant001{at}mc.duke.edu. Extracellular superoxide dismutase (SOD3) is the primary extracellular enzymatic scavenger of superoxide (O2-). SOD3's expression is highest in kidney, but its distribution and biological functions there are unknown. To investigate the function of renal SOD3, we co-localized it with erythropoietin (EPO) to proximal tubules using in situ hybridization and immunohistochemistry. We then exposed wild type (Wt) and SOD3 knockout (KO) mice to hypoxia and found a late hematocrit response in the KO strain. EPO mRNA expression was attenuated in KO mice during the first 6h of hypoxia preceded at 2 h by less accumulation of nuclear HIF-1 protein. Meanwhile KO mice exposed to hypoxia showed increases in renal mRNA for superoxide-producing NADPH oxidase (NOX4) and early significant increases in GSSG/GSH, a marker of oxidative stress, compared to Wt mice. Plasma nitrite/nitrate and renal 3-nitrotyrosine (3-NTyr), indicating peroxynitrite formation, increased later in hypoxia, and renal endothelial nitric oxide synthase protein induction was similar in both strains. These data show that hypoxic activation of HIF-1 and its target gene EPO in mouse kidney is regulated closely by the oxidant/antioxidant equilibrium involving SOD3, thus identifying renal SOD3 as a regulatory element in the body's innate adaptation to hypoxia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Ganguly, M. Depner, C. Fattman, K. Bein, T. D. Oury, S. C. Wesselkamper, M. T. Borchers, M. Schreiber, F. Gao, E. von Mutius, et al. Superoxide dismutase 3, extracellular (SOD3) variants and lung function Physiol Genomics, May 13, 2009; 37(3): 260 - 267. [Abstract] [Full Text] [PDF] N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF] E. Nozik-Grayck, H. B. Suliman, S. Majka, J. Albietz, Z. Van Rheen, K. Roush, and K. R. Stenmark Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodeling Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L422 - L430. [Abstract] [Full Text] [PDF] K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF] K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors Am J Physiol Renal Physiol, November 1, 2006; 291(5): F932 - F944. [Abstract] [Full Text] [PDF] M. Geiszt NADPH oxidases: New kids on the block Cardiovasc Res, July 15, 2006; 71(2): 289 - 299. [Abstract] [Full Text] [PDF] Y. Chen, P. S. Gill, and W. J. Welch Oxygen availability limits renal NADPH-dependent superoxide production Am J Physiol Renal Physiol, October 1, 2005; 289(4): F749 - F753. [Abstract] [Full Text] [PDF] M. Geiszt and T. L. Leto The Nox Family of NAD(P)H Oxidases: Host Defense and Beyond J. Biol. Chem., December 10, 2004; 279(50): 51715 - 51718. [Full Text] [PDF]

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