Glucocorticoid effects on the embryonic chick heart. II. Alteration of oxidative metabolism.
The injection of cortisol phosphate (0.5 mg per egg) onto the chorioallantoic membrane of embryonic chicks at 12 days incubation depresses the rate of oxygen consumption in heart mitochondria isolated from the chicks 24 or 48 hours after the injection as compared to a saline injected control. The oxygen consumption is depressed using either reduced nicotinamide-adenine dinucleotide (NADH)-linked or flavin adenine dinucleotide (FADH)-linked substrates. The progressive inhibition of oxidation and adenosine triphosphate (ATP) production rate is related to the time after cortisol is injected. The treated mitochondria appear to function differently when NADH-linked and FADH-linked respiratory substrates are compared. Using NADH-linked substrates (site 1), adenosine diphosphate (ADP) was phosphorylated by mitochondria, even though the rate of phosphorylation was decreased; however, when FADH-linked substrates were used, incomplete phosphorylation was observed. The rate and the extent of calcium accumulation by embryonic chick heart mitochondria were also depressed by cortisol. These data suggest a defect in phosphorylation at site 2 following cortisol treatment but not at the site 1 linked energy transducing step. Whether these impairments of mitochondrial function result from catabolic turnover of the mitochondrial membrane components, excessive calcium accumulation by the mitochondria, or from the digestion of mitochondrial constituents, has not been delineated.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002642:Chick Embryo / Q000378:metabolism*; D003864:Depression, Chemical; D006854:Hydrocortisone / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010766:Phosphorylation
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D006854:Hydrocortisone