RGD Reference Report - Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis.

Authors: Son, D  Kojima, I  Inagi, R  Matsumoto, M  Fujita, T  Nangaku, M 
Citation: Son D, etal., Am J Physiol Renal Physiol. 2008 Jan;294(1):F62-72. Epub 2007 Oct 24.
RGD ID: 8655955
Pubmed: PMID:17959751   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00113.2007   (Journal Full-text)

Accumulating evidence suggests a pathogenic role of chronic hypoxia in various kidney diseases. Chronic hypoxia in the kidney was induced by unilateral renal artery stenosis, followed 7 days later by observation of tubulointerstitial injury. Proteomic analysis of the hypoxic kidney found various altered proteins. Increased proteins included lipocortin-5, calgizzarin, ezrin, and transferrin, whereas the decreased proteins were alpha(2u)-globulin PGCL1, eukaryotic translation elongation factor 1alpha(2), and Cu/Zn superoxide dismutase (SOD1). Among these proteins, we focused on Cu/Zn-SOD, a crucial antioxidant. Western blot analysis and real-time quantitative PCR analysis confirmed the downregulation of Cu/Zn-SOD in the chronic hypoxic kidney. Furthermore, our laser capture microdissection system showed that the expression of Cu/Zn-SOD was predominant in the tubulointerstitium and was decreased by chronic hypoxia. The tubulointerstitial injury estimated by histology and immunohistochemical markers was ameliorated by tempol, a SOD mimetic. This amelioration was associated with a decrease in levels of the oxidative stress markers 4-hydroxyl-2-nonenal and nitrotyrosine. Our in vitro studies utilizing cultured tubular cells revealed a role of TNF-alpha in downregulation of Cu/Zn-SOD. Since the administration of anti-TNF-alpha antibody ameliorated Cu/Zn-SOD suppression, TNF-alpha seems to be one of the suppressants of Cu/Zn-SOD. In conclusion, our proteomic analysis revealed a decrease in Cu/Zn-SOD, at least partly by TNF-alpha, in the chronic hypoxic kidney. This study, for the first time, uncovered maladaptive suppression of Cu/Zn-SOD as a mediator of a vicious cycle of oxidative stress and subsequent renal injury induced by chronic hypoxia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SOD1Humanrenal artery obstruction  ISOSod1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 
Sod1Ratrenal artery obstruction  IEP protein:decreased expression:kidney (rat)RGD 
Sod1Mouserenal artery obstruction  ISOSod1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information