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Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia.

Publication ,  Journal Article
Suliman, HB; Ali, M; Piantadosi, CA
Published in: Blood
July 1, 2004

Extracellular superoxide dismutase (SOD3) is the primary extracellular enzymatic scavenger of superoxide ((.)O(2)(-)). SOD3's expression is highest in the kidney, but its distribution and biologic functions there are unknown. To investigate the function of renal SOD3, we colocalized it with erythropoietin (EPO) to proximal tubules using in situ hybridization and immunohistochemistry. We then exposed wild-type (Wt) and SOD3 knock-out (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 6 hours of hypoxia preceded at 2 hours by less accumulation of nuclear hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) protein. Meanwhile KO mice exposed to hypoxia showed increases in renal mRNA for superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4) and early significant increases in glutathione disulfide (GSSG)/glutathione (GSH), a marker of oxidative stress, compared with 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 alpha 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.

Duke Scholars

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

July 1, 2004

Volume

104

Issue

1

Start / End Page

43 / 50

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Superoxide Dismutase
  • RNA, Messenger
  • Oxidative Stress
  • Nitrites
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide
 

Citation

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Suliman, H. B., Ali, M., & Piantadosi, C. A. (2004). Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood, 104(1), 43–50. https://doi.org/10.1182/blood-2003-07-2240
Suliman, Hagir B., Mervat Ali, and Claude A. Piantadosi. “Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia.Blood 104, no. 1 (July 1, 2004): 43–50. https://doi.org/10.1182/blood-2003-07-2240.
Suliman HB, Ali M, Piantadosi CA. Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood. 2004 Jul 1;104(1):43–50.
Suliman, Hagir B., et al. “Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia.Blood, vol. 104, no. 1, July 2004, pp. 43–50. Pubmed, doi:10.1182/blood-2003-07-2240.
Suliman HB, Ali M, Piantadosi CA. Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood. 2004 Jul 1;104(1):43–50.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

July 1, 2004

Volume

104

Issue

1

Start / End Page

43 / 50

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Superoxide Dismutase
  • RNA, Messenger
  • Oxidative Stress
  • Nitrites
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide