Relative importance of intracellular glutathione peroxidase and catalase in vivo for prevention of peroxidation to the heart.
The relative importance in vivo of catalase and the selenoenzyme glutathione peroxidase for protection against peroxidation was assessed in the rat heart. Each of these enzymes was modulated by feeding animals a low selenium diet either unsupplemented or supplemented with 0.5 parts per million of selenium, with or without the catalase inhibitor, 3-amino-1,2,4-triazole, in their drinking water. After 8 weeks, selenium deficient rats had 88% reductions in cytosolic and mitochondrial glutathione peroxidase activities. These reductions were accompanied by increased peroxidation in heart homogenates and mitochondrial suspensions. Since increased mitochondrial peroxidation only occurred when both the cytosolic and mitochondrial glutathione peroxidase activities were compromised, these selenoenzymes appear to work in tandem and reductions in both are a prerequisite for increased peroxidation in this organ. Peroxidation did not occur in aminotriazole treated animals even though cytosolic catalase activity was inhibited by 65-80%. Moreover, inhibition of catalase activity did not exacerbate the level of peroxidation in selenium deficient animals depleted of glutathione peroxidase activity. Because increased peroxidation was only associated with reductions in glutathione peroxidase activity irrespective of catalase activity, the selenoenzyme appears to be more important for detoxification of hydrogen peroxide in the heart.
Simmons
T W
TW
Toxicology Program, St. John's University, Jamaica, New York.
Jamall
I S
IS
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004032:Diet; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage
D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D012643:Selenium; D000640:Amitrole