Expression of catalase and glutathione peroxidase in renal insufficiency.
Chronic renal failure (CRF) is associated with oxidative stress, the precise mechanism of which is yet to be elucidated. The present study was undertaken to investigate in renal insufficiency the expression of catalase and glutathione peroxidase, which play a critical role in antioxidant defense system by catalyzing detoxification of hydrogen peroxide (H2O2) and organic hydroperoxides. Rats were randomly assigned to the CRF (5/6 nephrectomized) and sham-operated control groups and observed for 6 weeks. Renal and thoracic aortic catalase and glutathione peroxidase protein abundance was measured by Western blotting. The enzyme activities in the renal and aortic extracts, hepatic glutathione levels, blood pressure and urinary nitric oxide metabolites (NO(x)) excretion were also measured. Blood pressure and urinary nitric oxide metabolite (NO(x)) excretion were also measured. The CRF group showed a significant down-regulation of both immunodetectable catalase and glutathione peroxidase proteins in the remnant kidney. Catalase activity was also significantly decreased in the remnant kidney whereas glutathione peroxidase activity was not significantly affected. Furthermore, the protein abundance of catalase was unchanged whereas the enzyme activity was significantly decreased in the thoracic aorta of CRF animals compared to the sham-operated controls. By contrast, both the protein abundance and the enzyme activity of glutathione peroxidase were not significantly affected in the aorta of CRF animals compared to the sham-operated controls. This was coupled with marked arterial hypertension, significant reduction of hepatic glutathione levels and urinary NO(x) excretion pointing to increased inactivation and sequestration of NO by superoxide. These events point to the role of impaired antioxidant defense system in the pathogenesis of oxidative stress in CRF.
Sindhu
Ram K
RK
Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, University of California at Irvine, Irvine, CA 92697-4066, USA. rasindhu@cdrewu.edu
Ehdaie
Ashkan
A
Farmand
Farbod
F
Dhaliwal
Kanwaljit K
KK
Nguyen
Tri
T
Zhan
Chang-De
CD
Roberts
Christian K
CK
Vaziri
Nosratola D
ND
D000818:Animals; D001011:Aorta / Q000201:enzymology; D001013:Aorta, Thoracic / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000378:metabolism*; D015854:Up-Regulation
D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione