Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1985 Feb 15;226(1):155–161. doi: 10.1042/bj2260155

The respiration and calcium content of heart mitochondria from rats with vitamin D-induced cardionecrosis.

M M Zydowo, J Swierczyński, G Nagel, T Wrzołkowa
PMCID: PMC1144688  PMID: 2983684

Abstract

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.

Full text

PDF
155

Images in this article

158Fig. 1.
on p.158

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borle A. B. Control, Modulation, and regulation of cell calcium. Rev Physiol Biochem Pharmacol. 1981;90:13–153. doi: 10.1007/BFb0034078. [DOI] [PubMed] [Google Scholar]
  2. Buja L. M., Dees J. H., Harling D. F., Willerson J. T. Analytical electron microscopic study of mitochondrial inclusions in canine myocardial infarcts. J Histochem Cytochem. 1976 Mar;24(3):508–516. doi: 10.1177/24.3.57191. [DOI] [PubMed] [Google Scholar]
  3. De Luca H. F., Paaren H. E., Schnoes H. K. Vitamin D and calcium metabolism. Top Curr Chem. 1979;83:1–65. doi: 10.1007/BFb0019662. [DOI] [PubMed] [Google Scholar]
  4. HEGGTVEIT H. A., HERMAN L., MISHRA R. K. CARDIAC NECROSIS AND CALCIFICATION IN EXPERIMENTAL MAGNESIUM DEFICIENCY. A LIGHT AND ELECTRON MICROSCOPIC STUDY. Am J Pathol. 1964 Nov;45:757–782. [PMC free article] [PubMed] [Google Scholar]
  5. Jacobus W. E., Tiozzo R., Lugli G., Lehninger A. L., Carafoli E. Aspects of energy-linked calcium accumulation by rat heart mitochondria. J Biol Chem. 1975 Oct 10;250(19):7863–7870. [PubMed] [Google Scholar]
  6. Jennings R. B., Moore C. B., Shen A. C., Herdson P. B. Electrolytes of damaged myocardial mitochondria. Proc Soc Exp Biol Med. 1970 Nov;135(2):515–522. doi: 10.3181/00379727-135-35086. [DOI] [PubMed] [Google Scholar]
  7. Kessar P., Crompton M. The sequestration of Ca2+ by mitochondria in rat heart cells. Cell Calcium. 1983 Oct;4(4):295–305. doi: 10.1016/0143-4160(83)90006-4. [DOI] [PubMed] [Google Scholar]
  8. Mukherjee A., Zerwekh J. E., Nicar M. J., McCoy K., Buja L. M. Effect of chronic vitamin D deficiency on chick heart mitochondrial oxidative phosphorylation. J Mol Cell Cardiol. 1981 Feb;13(2):171–183. doi: 10.1016/0022-2828(81)90214-5. [DOI] [PubMed] [Google Scholar]
  9. RONA G., CHAPPEL C. I., BALAZS T., GAUDRY R. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959 Apr;67(4):443–455. [PubMed] [Google Scholar]
  10. Reinhart P. H., van de Pol E., Taylor W. M., Bygrave F. L. An assessment of the calcium content of rat liver mitochondria in vivo. Biochem J. 1984 Mar 1;218(2):415–420. doi: 10.1042/bj2180415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. SLATER E. C., CLELAND K. W. The effect of calcium on the respiratory and phosphorylative activities of heart-muscle sarcosomes. Biochem J. 1953 Nov;55(4):566–590. doi: 10.1042/bj0550566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Urbánek E., Vasků J., Bednarík B., Praslicka M., Pospísil Electrolyte changes in myocardial injury. Recent Adv Stud Cardiac Struct Metab. 1975;6:43–58. [PubMed] [Google Scholar]
  13. Williamson J. R., Williams R. J., Coll K. E., Thomas A. P. Cytosolic free Ca2+ concentration and intracellular calcium distribution of Ca2+-tolerant isolated heart cells. J Biol Chem. 1983 Nov 25;258(22):13411–13414. [PubMed] [Google Scholar]
  14. Wrogemann K., Blanchaer M. C., Jacobson B. E. Oxidative phosphorylation in cardiomyopathic hamsters. Am J Physiol. 1972 Jun;222(6):1453–1457. doi: 10.1152/ajplegacy.1972.222.6.1453. [DOI] [PubMed] [Google Scholar]
  15. Wrogemann K., Jacobson B. E., Blanchaer M. C. On the mechanism of a calcium-associated defect of oxidative phosphorylation in progessive muscular dystrophy. Arch Biochem Biophys. 1973 Nov;159(1):267–278. doi: 10.1016/0003-9861(73)90453-0. [DOI] [PubMed] [Google Scholar]
  16. Wrogemann K., Nylen E. G. Mitochondrial calcium overloading in cardiomyopathic hamsters. J Mol Cell Cardiol. 1978 Feb;10(2):185–195. doi: 10.1016/0022-2828(78)90042-1. [DOI] [PubMed] [Google Scholar]
  17. Wrogemann K., Pena S. D. Mitochondrial calcium overload: A general mechanism for cell-necrosis in muscle diseases. Lancet. 1976 Mar 27;1(7961):672–674. doi: 10.1016/s0140-6736(76)92781-1. [DOI] [PubMed] [Google Scholar]
  18. Wrzołkowa T., Zydowo M., Tyburska I., Lukaszyk I. Experimental atherosclerosis of the rat heart muscle. Acta Med Pol. 1979;20(1):51–52. [PubMed] [Google Scholar]
  19. Wrzołkowa T., Zydowo M. Ultrastructural studies on the vitamin D induced heart lesions in the rat. J Mol Cell Cardiol. 1980 Oct;12(10):1117–1133. doi: 10.1016/0022-2828(80)90036-x. [DOI] [PubMed] [Google Scholar]
  20. Zydowo M., Walentynowicz O., Wrzołkowa T. AMP deaminase from the rat heart injured by high doses of vitamin D. Acta Biochim Pol. 1980;27(3-4):233–240. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES