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Department of Medicine, Division of Gastroenterology and Nutrition, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284
Selenium deficiency has been implicated as a cause of the cardiomyopathy known as Keshan disease in China. Selenium is an essential constituent of glutathione peroxidase, an enzyme that destroys hydroperoxides by using the reducing equivalents of reduced glutathione (GSH). We studied glutathione-dependent hydroperoxide metabolism in isolated perfused rat hearts. Hearts from selenium-deficient rats contained 5% of the glutathione peroxidase activity found in control hearts. Glutathione reductase activity and glutathione content were not affected by selenium deficiency. Infusion of t-butylhydroperoxide into control hearts caused an increase in heart glutathione disulfide (GSSG) concentration proportional to the rate of hydroperoxide infusion up to 200 nmol/(g heart · min). GSSG was released into the perfusate in proportion to the hydroperoxide infusion rate up to 150 nmol/(g heart · min), but GSSG release did not increase further with higher infusion rates. Thus, GSSG release by the heart is saturable. It had a maximum rate of about 14 nmol GSH equivalents/(g heart · min) when stimulated by t-butylhydroperoxide infusion. This indicates that GSSG release by the heart is carrier-mediated and is not due to passive diffusion. Infusion of hydroperoxide into selenium-deficient hearts failed to cause increases in heart GSSG concentration and in GSSG release. This indicates that selenium-deficient heart cannot metabolize hydroperoxides through glutathione-dependent pathways. We suggest that selenium deficiency might predispose the heart to injury from oxidant stress.
KEY WORDS: selenium Keshan disease cardiomyopathy glutathione hydroperoxide metabolism
1 Supported by NIH Grant ES 02497 and Grant No. AQ-870 from the Robert A. Welch Foundation of Houston, Texas.
2 Dr. Xia was a Visiting Scientist during these studies. Her present address is Institute of Health, China National Center for Preventive Medicine, 29 Nan Wei Road, Beijing, China.
3 To whom reprint requests should be addressed.
Manuscript received 13 August 1984. Revision accepted 20 February 1985.
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