Altered oxidative metabolism in selenium-deficient rat granulocytes.
Rats fed a selenium-deficient diet for 12 to 15 wk became selenium-depleted, measured by the selenium content of liver and granulocytes. The activity of granulocyte glutathione peroxidase, a selenoenzyme, in deficient rats was 11% of the activity in replete rat granulocytes. When stimulated with an H2O2 generating system, the HMPS activity of the deficient granulocytes was 50% of replete; however, when stimulated with methylene blue, the HMPS activity in deficient and replete granulocytes was the same. When granulocytes were incubated with PMA or OPZ, deficient granulocytes initially had the same O-2-generating activity as replete granulocytes; however, with increasing duration of stimulation, granulocytes from deficient rats generated less O-2 than replete rats. After 20 min in an H2O2-generating system, deficient granulocytes stimulated with PMA or OPZ generated less O-2 than replete granulocytes. These results indicate that deficient granulocytes did not metabolize H2O2 as well as replete granulocytes and that H2O2 caused damage to the O2-generating system. Measurement of O-2 generation in membrane-enriched particles showed the above effects were due to inactivation of the NADPH-dependent O2-generating system. Deficient granulocytes stimulated with OPZ for 20 min had 70% less membrane O-2-generating activity than controls. In addition, when membrane-enriched particles were made from cells that had been stressed with an H2O2-generating system, NADPH-dependent O-2-generating activity in deficient granulocytes was 50% of replete. In selenium-deficient granulocytes with low GSH-Px activity, prolonged incubation with stimulants and prior incubations with an H2O2-generating system caused loss of activity of the membrane-bound, NADPH-dependent, O-2-generating system.
D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D006098:Granulocytes / Q000201:enzymology / Q000378:metabolism*; D006600:Hexosephosphates / Q000378:metabolism; D008099:Liver / Q000032:analysis / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000172:deficiency*; D013481:Superoxides / Q000096:biosynthesis; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D015054:Zymosan / Q000494:pharmacology
D006600:Hexosephosphates; D013481:Superoxides; D014810:Vitamin E; D009249:NADP; D015054:Zymosan; D005979:Glutathione Peroxidase; D012643:Selenium