Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation.
The administration of dexamethasone to rats markedly diminished the initial rate and maximal extent of substrate-dependent calcium uptake in subsequently isolated liver mitochondria, and enhanced the release of calcium. The apparent Km for calcium transport was not altered by dexamethasone treatment and it ranged from 50 to 80 muM when an EDTA/Ca buffer system was used in the presence of magnesium, and 20 muM when an NTA/Ca buffer system without magnesium was employed. In contrast, when ATP was employed as the energy source, there was no significant difference in initial rate, Km, or the extent of calcium accumulation between mitochondria from control and dexamethasone-treated animals. Although mitochondria from dexamethasone-treated animal showed 15% less cytochrome c oxidase activity/mg of protein, overall respiratory capacity and ATP production from ADP were the same as in control mitochondria. However, mitochondria from dexamethasone-treated animals translocated ATP from inside to outside faster than those from control animals. When the ATP in the medium was depleted by glucose and hexokinase, both types of mitochondria retained essentially all the preloaded calcium until total ATP reached a critical level (7 approximately 5 mumol of ATP/mg of protein). When ATP content fell below this critical level, mitochondria released all the calcium quickly. Dexamethasone treatment increased the susceptibility of mitochondria to the depletion of ATP. These data indicate that the dexamethasone-induced decrease in maximal calcium transport and in calcium retention carrier system per se, but o an altered ability of the mitochondria to regulate intramitochondrial ATP content.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D003575:Cytochromes c1 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D008954:Models, Biological; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D003574:Cytochrome c Group; D003580:Cytochromes; D000244:Adenosine Diphosphate; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D003575:Cytochromes c1; D000226:Mitochondrial ADP, ATP Translocases; D006593:Hexokinase; D009713:Nucleotidyltransferases; D005947:Glucose; D002118:Calcium