Selenite-induced NAD(P)H oxidation and calcium release in isolated mitochondria: relationship to in vivo toxicity.
The effects of selenite on the mitochondrial NAD(P)H/NAD(P) ratio and calcium pool are described. Small quantities of selenite can 1) oxidize mitochondrial NAD(P)H and 2) induce calcium release from isolated mitochondria. Reduced NAD(P)H within intact mitochondria was monitored kinetically using the wavelength pair, 340-375 nm. NAD(P)H oxidation rates at various concentrations of selenite were calculated. Mitochondria from older animals can oxidize NAD(P)H faster than those of younger animals; maximum selenite-induced oxidation rates correlate well with age of the animal in both kidney (r = 0.920) and liver (r = 0.839) mitochondria, the oxidation rates in the adult (liver 15.4, kidney 34.8 nmol/min/mg of protein) being 3-5 times the rates in the 1- to 2-day-old newborn (liver 2.8, kidney 10.3 nmol/min/mg protein). Calcium fluxes within mitochondrial suspensions were monitored kinetically using the calcium indicator, Arsenazo III, and the wavelength pair, 660-685 nm. Susceptibility to selenite-induced calcium release is age dependent, the mitochondria of older animals being more susceptible. Incubation time required to induce calcium release was 77 +/- 30 sec in the adult compared to 406 +/- 25 sec at the age of 0-4 days in the newborn. The bimodal toxic manifestations of selenite in vivo are discussed in view of the age-dependent differences in selenite metabolism at the cellular level.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D007668:Kidney / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000254:growth & development; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology* / Q000633:toxicity
D009243:NAD; D009249:NADP; D020887:Selenious Acid; D012643:Selenium; D002118:Calcium