Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase.
Previous studies from this laboratory have demonstrated the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension. This study was designed to determine whether oxidative stress in animals with lead-induced hypertension is associated with dysregulation of the activities of the main antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). In addition, we aimed to determine the effect of lead on the regulation of guanylate cyclase (GC) expression. Male Sprague-Dawley rats were randomly assigned to control and lead-exposed groups, and immunodetectable Cu/Zn SOD, Mn SOD, CAT, and GPX were determined by immunoblotting in the thoracic aorta. Additionally, the activities of these enzymes were measured in the renal cortex, medulla, and thoracic aorta. Furthermore, immunodetectable GC was determined in the thoracic aorta. In the thoracic aorta, lead exposure resulted in significant upregulation of aortic Cu/Zn SOD activity, while CAT and GPX activity and CuZn SOD, Mn SOD, and CAT protein abundance were unchanged. Conversely, GC protein abundance was decreased in thoracic aorta. In renal cortex and medulla, CAT and Cu/Zn SOD activities were increased, while GPX activity was unchanged. Lead-exposed animals exhibited upregulation of some antioxidant enzyme activities, most likely as a compensatory response to lead exposure. However, other enzymes did not compensate in the face of oxidative stress, suggestive of an antioxidant/oxidant imbalance. These findings, combined with decrease in aortic GC protein abundance, provide further evidence for dysregulation of antioxidant/oxidant balance and hypertension in this model.
Farmand
Farbod
F
Division of Nephrology and Hypertension, Department of Medicine, College of Medicine, University of California, Irvine, CA 92697-4066, USA.
Ehdaie
Ashkan
A
Roberts
Christian K
CK
Sindhu
Ram K
RK
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
D007854:Lead; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase