Role of intracellular SOD in oxidant-induced injury to normal and copper-deficient cardiac myocytes.
Previous studies have shown that susceptibilities of hepatocytes and endothelial cells to H2O(2)-induced injury are altered by changes in the intracellular activity of Cu,Zn-containing superoxide dismutase (CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in oxidant-induced injury to rat cardiac myocytes, cells with reduced CuZn-SOD activity but normal ATP content were either isolated from the hearts of adult copper-deficient rats or obtained by treatment of normal isolated adult myocytes with diethyldithiocarbamate. These myocytes and controls with normal CuZn-SOD activity were exposed to either reagent H2O2 or oxidants generated by extracellular glucose oxidase plus glucose or xanthine oxidase plus xanthine. It was shown that myocytes with CuZn-SOD activities reduced by 70-90% were equally susceptible to H2O2 and the two oxidant-generating systems as the control myocytes. The findings suggest that in adult cardiac myocytes, in contrast to the situation in some other cells, intracellular CuZn-SOD may not have a significant defensive role against acute H2O(2)-induced injury. The possibility remains, however, that changes in the activity of this enzyme, e.g., in copper deficiency, may be relevant to the ability of myocytes to cope with chronic oxidative stress resulting from imbalance between intracellular oxygen radical-generating and -scavenging systems.
Sarvazyan
N
N
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Askari
A
A
Klevay
L M
LM
Askari
A
A
Huang
W H
WH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003300:Copper / Q000172:deficiency*; D004050:Ditiocarb / Q000494:pharmacology; D005949:Glucose Oxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D003300:Copper; D000255:Adenosine Triphosphate; D004050:Ditiocarb; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase