The respiration and calcium content of heart mitochondria from rats with vitamin D-induced cardionecrosis.
Mitochondria were isolated from the heart and skeletal muscle of rats treated with three consecutive daily doses of 100 000 i.u. of calciol (cholecalciferol; 'vitamin D3'). On the fourth day after the last dose, cardiac necrosis developed. At that time mitochondria isolated from heart displayed a 10-fold higher Ca2+ content and a 6-fold lower respiratory rate with pyruvate-plus-malate as substrate as well as with other NAD-dependent substrates. No decrease in respiratory rate with succinate as substrate was observed. EDTA (5 mM) added to the medium during the isolation procedure restored both the high respiratory rate with pyruvate + malate and the low Ca2+ content of the heart mitochondria. The addition of 1 mM-CaCl2 to the medium in which a healthy (control) rat heart had been homogenized caused the same impairment of the mitochondria as did calciol treatment of the animals. No changes of mitochondria isolated from skeletal muscle were observed in rats treated with calciol. It is concluded that the heart mitochondria in vivo fail to accumulate Ca2+ from the cardiac cell overloaded with Ca2+ as the consequence of calciol treatment. Mitochondrial Ca2+ accumulation occurs during the isolation procedure unless an appropriate amount of chelating agent is added to the homogenization medium. The implication of these findings for the biochemical sequence of events in the calciol-induced cardiac necrosis is discussed.
Zydowo
M M
MM
Swierczyński
J
J
Nagel
G
G
Wrzołkowa
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002762:Cholecalciferol; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D009132:Muscles / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D002762:Cholecalciferol; D002118:Calcium