Differential effects of 2,4-dinitrophenol and valinomycin (+ K+) on uncoupler-stimulated ATPase of human tumor mitochondria.
The uncoupler-stimulated mitochondrial ATPase of four human tumors, mouse kidney, brain and fetal liver exhibited a characteristic behavior when preincubated with the H+-conducting uncouplers, dinitrophenol, CCCP, S-13 and gramicidin. The ATPase activity was considerably lower with preincubation than without. Preincubation with valinomycin (+ K+), on the other hand, did not result in a significant decrease of the ATPase activity. These results may be contrasted with those obtained with liver or heart mitochondria, the ATPase activity of which did not suffer any loss when preincubated with dinitrophenol. The effect of preincubation with dinitrophenol on the tumor mitochondria could not be accounted for by dinitrophenol-induced Mg2+ efflux, since the differential effects of dinitrophenol and valinomycin (+ K+) remained even when ATPase activity was determined in presence of Mg2+. Small amounts of ATP and ADP in the preincubation mixture containing dinitrophenol protected against the decay of the ATPase activity, implicating the exchangeable adenine nucleotides in the tumor mitochondria. In a model system where liver mitochondria were depleted of their adenine nucleotides, a lower ATPase activity was indeed obtained. However, direct determination of the concentrations of adenine nucleotides in dinitrophenol- and valinomycin-treated tumor mitochondria revealed only slight differences.
D019297:2,4-Dinitrophenol; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001254:Astrocytoma / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D018288:Carcinoma, Small Cell / Q000201:enzymology; D002460:Cell Line; D004140:Dinitrophenols / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology*; D014475:Uncoupling Agents / Q000494:pharmacology*; D014634:Valinomycin / Q000494:pharmacology*
D004140:Dinitrophenols; D014475:Uncoupling Agents; D014634:Valinomycin; D000251:Adenosine Triphosphatases; D019297:2,4-Dinitrophenol