Hydroperoxide-stimulated release of calcium from rat liver and AS-30D hepatoma mitochondria.
The presence of 50 microM t-butyl hydroperoxide induces the oxidation of intramitochondrial pyridine nucleotides and release of accumulated Ca2+ from rat liver but not AS-30D hepatoma mitochondria in the presence of succinate (plus rotenone) as a respiratory substrate. The effects of t-butyl hydroperoxide are mediated by the activities of glutathione peroxidase and reductase, which are less than 20 and 50% as active, respectively, in hepatoma than in normal liver mitochondria. However, the differences in the activities of these enzymes are not responsible for the insensitivity of succinate-energized tumor mitochondria to t-butyl hydroperoxide, since Ca2+ release and pyridine nucleotide oxidation can be elicited when ascorbate plus tetramethyl-p-phenylenediamine are used as alternative respiratory electron donors. In the presence of succinate alone, rat liver mitochondria generate malate exclusively, whereas AS-30D hepatoma mitochondria produce pyruvate and reduced nicotinamide adenine dinucleotide phosphate as well as malate due to the activity of a nicotinamide adenine dinucleotide phosphate-dependent malic enzyme which is not present in normal rat liver mitochondria. These results indicate that the maintenance of pyridine nucleotides in their reduced form by malic enzyme is responsible for the lack of t-butyl hydroperoxide-induced Ca2+ efflux by tumor mitochondria respiring on succinate. This altered pattern of mitochondrial metabolism may also influence the regulation of other reduced nicotinamide adenine dinucleotide phosphate-sensitive activities in addition to that of Ca2+ transport.
Fiskum
G
G
Pease
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013386:Succinates / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D008293:Malates; D010545:Peroxides; D011773:Pyruvates; D013386:Succinates; D009243:NAD; D009249:NADP; D020122:tert-Butylhydroperoxide; D008291:Malate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D002118:Calcium