Abstract
Cytochrome-c-oxidase, the terminal enzyme of the respiratory chain, was studied in 140 hearts from men obtained at autopsy revealing randomly distributed cardiomyocytes without enzyme activity. The expression of the defect was independent of an underlying heart disease and was observed both in normal hearts and in hearts with hypertrophy and/or coronary arteriosclerosis. In contrast, age was a discriminating factor: The defects occurred sporadically in the second decade, but were regularly present from the sixth decade on. Also, the number of defects/sq cm (defect density) increased with age from 2 to 3 in the second and third decade, to about 50 defects in advanced age. Irrespective of the defect density, the enzyme defect always affected isolated cardiomyocytes and ended abruptly at the intercalated disc of neighboring heart muscle cells, as revealed by ultracytochemistry. The results indicate that cytochrome-c-oxidase deficient heart muscle cells represent a degenerative lesion associated with cellular ageing and may be involved in the reduction of myocardial contractile ability in senescence.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abu-Erreish G. M., Sanadi D. R. Age-related changes in cytochrome concentration of myocardial mitochondria. Mech Ageing Dev. 1978 Jun;7(6):425–432. doi: 10.1016/0047-6374(78)90083-0. [DOI] [PubMed] [Google Scholar]
- Anversa P., Hiler B., Ricci R., Guideri G., Olivetti G. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J Am Coll Cardiol. 1986 Dec;8(6):1441–1448. doi: 10.1016/s0735-1097(86)80321-7. [DOI] [PubMed] [Google Scholar]
- Bastiaensen L. A., Joosten E. M., de Rooij J. A., Hommes O. R., Stadhouders A. M., Jaspar H. H., Veerkamp J. H., Bookelman H., van Hinsbergh V. W. Ophthalmoplegia-plus, a real nosological entity. Acta Neurol Scand. 1978 Jul;58(1):9–34. doi: 10.1111/j.1600-0404.1978.tb02856.x. [DOI] [PubMed] [Google Scholar]
- Bender F. Klinik des alternden Herzens. Z Kardiol. 1985;74 (Suppl 7):49–54. [PubMed] [Google Scholar]
- Berenberg R. A., Pellock J. M., DiMauro S., Schotland D. L., Bonilla E., Eastwood A., Hays A., Vicale C. T., Behrens M., Chutorian A. Lumping or splitting? "Ophthalmoplegia-plus" or Kearns-Sayre syndrome? Ann Neurol. 1977 Jan;1(1):37–54. doi: 10.1002/ana.410010104. [DOI] [PubMed] [Google Scholar]
- Byrne E., Dennett X., Trounce I., Henderson R. Partial cytochrome oxidase (aa3) deficiency in chronic progressive external ophthalmoplegia. Histochemical and biochemical studies. J Neurol Sci. 1985 Dec;71(2-3):257–271. doi: 10.1016/0022-510x(85)90064-4. [DOI] [PubMed] [Google Scholar]
- Davies M. J., Pomerance A. Quantitative study of ageing changes in the human sinoatrial node and internodal tracts. Br Heart J. 1972 Feb;34(2):150–152. doi: 10.1136/hrt.34.2.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiMauro S., Bonilla E., Zeviani M., Nakagawa M., DeVivo D. C. Mitochondrial myopathies. Ann Neurol. 1985 Jun;17(6):521–538. doi: 10.1002/ana.410170602. [DOI] [PubMed] [Google Scholar]
- DiMauro S., Zeviani M., Bonilla E., Bresolin N., Nakagawa M., Miranda A. F., Moggio M. Cytochrome c oxidase deficiency. Biochem Soc Trans. 1985 Aug;13(4):651–653. doi: 10.1042/bst0130651. [DOI] [PubMed] [Google Scholar]
- DiMauro S., Zeviani M., Rizzuto R., Lombes A., Nakase H., Bonilla E., Miranda A., Schon E. Molecular defects in cytochrome oxidase in mitochondrial diseases. J Bioenerg Biomembr. 1988 Jun;20(3):353–364. doi: 10.1007/BF00769637. [DOI] [PubMed] [Google Scholar]
- DiMauro S., Zeviani M., Servidei S., Bonilla E., Miranda A. F., Prelle A., Schon E. A. Cytochrome oxidase deficiency: clinical and biochemical heterogeneity. Ann N Y Acad Sci. 1986;488:19–32. doi: 10.1111/j.1749-6632.1986.tb46545.x. [DOI] [PubMed] [Google Scholar]
- Ehsani A. A. Cardiovascular adaptations to exercise training in the elderly. Fed Proc. 1987 Apr;46(5):1840–1843. [PubMed] [Google Scholar]
- Fleming J. E., Miquel J., Cottrell S. F., Yengoyan L. S., Economos A. C. Is cell aging caused by respiration-dependent injury to the mitochondrial genome? Gerontology. 1982;28(1):44–53. doi: 10.1159/000212510. [DOI] [PubMed] [Google Scholar]
- Freeman B. A., Crapo J. D. Biology of disease: free radicals and tissue injury. Lab Invest. 1982 Nov;47(5):412–426. [PubMed] [Google Scholar]
- Frenzel H. Das Herz im Alter. Licht- und elektronenmikroskopische Befunde. Z Kardiol. 1985;74 (Suppl 7):17–25. [PubMed] [Google Scholar]
- Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol. 1983;23:239–257. doi: 10.1146/annurev.pa.23.040183.001323. [DOI] [PubMed] [Google Scholar]
- Fujino M., Okada R., Arakawa K. The relationship of aging to histological changes in the conduction system of the normal human heart. Jpn Heart J. 1983 Jan;24(1):13–20. doi: 10.1536/ihj.24.13. [DOI] [PubMed] [Google Scholar]
- Gerstenblith G., Lakatta E. G., Weisfeldt M. L. Age changes in myocardial function and exercise response. Prog Cardiovasc Dis. 1976 Jul-Aug;19(1):1–21. doi: 10.1016/0033-0620(76)90005-0. [DOI] [PubMed] [Google Scholar]
- Halliwell B., Gutteridge J. M. The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med. 1985;8(2):89–193. doi: 10.1016/0098-2997(85)90001-9. [DOI] [PubMed] [Google Scholar]
- Halliwell B. Oxygen radicals: a commonsense look at their nature and medical importance. Med Biol. 1984;62(2):71–77. [PubMed] [Google Scholar]
- Hayes D. J., Lecky B. R., Landon D. N., Morgan-Hughes J. A., Clark J. B. A new mitochondrial myopathy. Biochemical studies revealing a deficiency in the cytochrome b-c1 complex (complex III) of the respiratory chain. Brain. 1984 Dec;107(Pt 4):1165–1177. doi: 10.1093/brain/107.4.1165. [DOI] [PubMed] [Google Scholar]
- Hecht F. M. Studie über quantitative Altersveränderungen am Hisschen Bündel des Menschen. Virchows Arch A Pathol Anat Histol. 1980;386(3):343–356. doi: 10.1007/BF00427303. [DOI] [PubMed] [Google Scholar]
- Hegner D. Age-dependence of molecular and functional changes in biological membrane properties. Mech Ageing Dev. 1980 Sep-Oct;14(1-2):101–118. doi: 10.1016/0047-6374(80)90109-8. [DOI] [PubMed] [Google Scholar]
- Hollmann W., Rost R., Liesen H. Die Bedeutung des Sports für das Herz des ältern Menschen. Z Kardiol. 1985;74 (Suppl 7):39–48. [PubMed] [Google Scholar]
- Johnson M. A., Kadenbach B., Droste M., Old S. L., Turnbull D. M. Immunocytochemical studies of cytochrome oxidase subunits in skeletal muscle of patients with partial cytochrome oxidase deficiencies. J Neurol Sci. 1988 Oct;87(1):75–90. doi: 10.1016/0022-510x(88)90056-1. [DOI] [PubMed] [Google Scholar]
- Johnson M. A., Turnbull D. M., Dick D. J., Sherratt H. S. A partial deficiency of cytochrome c oxidase in chronic progressive external ophthalmoplegia. J Neurol Sci. 1983 Jul;60(1):31–53. doi: 10.1016/0022-510x(83)90125-9. [DOI] [PubMed] [Google Scholar]
- Kadenbach B., Jarausch J., Hartmann R., Merle P. Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure. Anal Biochem. 1983 Mar;129(2):517–521. doi: 10.1016/0003-2697(83)90586-9. [DOI] [PubMed] [Google Scholar]
- Kadenbach B. Regulation of respiration and ATP synthesis in higher organisms: hypothesis. J Bioenerg Biomembr. 1986 Feb;18(1):39–54. doi: 10.1007/BF00743611. [DOI] [PubMed] [Google Scholar]
- Kuhn-Nentwig L., Kadenbach B. Isolation and characterization of human heart cytochrome c oxidase. J Bioenerg Biomembr. 1986 Aug;18(4):307–314. doi: 10.1007/BF00743051. [DOI] [PubMed] [Google Scholar]
- Lakatta E. G. Alterations in the cardiovascular system that occur in advanced age. Fed Proc. 1979 Feb;38(2):163–167. [PubMed] [Google Scholar]
- Lakatta E. G. Cardiac muscle changes in senescence. Annu Rev Physiol. 1987;49:519–531. doi: 10.1146/annurev.ph.49.030187.002511. [DOI] [PubMed] [Google Scholar]
- Maron B. J., Ferrans V. J., Roberts W. C. Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am J Pathol. 1975 Jun;79(3):387–434. [PMC free article] [PubMed] [Google Scholar]
- Miquel J., Economos A. C., Fleming J., Johnson J. E., Jr Mitochondrial role in cell aging. Exp Gerontol. 1980;15(6):575–591. doi: 10.1016/0531-5565(80)90010-8. [DOI] [PubMed] [Google Scholar]
- Müller-Höcker J., Johannes A., Droste M., Kadenbach B., Pongratz D., Hübner G. Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome with deficiency of cytochrome-c-oxidase in cardiac and skeletal muscle. An enzymehistochemical--ultra-immunocytochemical--fine structural study in longterm frozen autopsy tissue. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;52(4):353–367. doi: 10.1007/BF02889977. [DOI] [PubMed] [Google Scholar]
- Müller-Höcker J., Pongratz D., Hübner G. Focal deficiency of cytochrome-c-oxidase in skeletal muscle of patients with progressive external ophthalmoplegia. Cytochemical-fine-structural study. Virchows Arch A Pathol Anat Histopathol. 1983;402(1):61–71. doi: 10.1007/BF00695049. [DOI] [PubMed] [Google Scholar]
- Müller-Höcker J., Stünkel S., Pongratz D., Hübner G. Focal deficiency of cytochrome c oxidase and of mitochondrial ATPase with histochemical evidence of loosely coupled oxidative phosphorylation in a mitochondrial myopathy of a patient with bilateral ptosis. An enzyme histochemical, immunocytochemical and fine structural study. J Neurol Sci. 1985 May-Jun;69(1-2):27–36. doi: 10.1016/0022-510x(85)90004-8. [DOI] [PubMed] [Google Scholar]
- Nohl H., Breuninger V., Hegner D. Influence of mitochondrial radical formation on energy-linked respiration. Eur J Biochem. 1978 Oct;90(2):385–390. doi: 10.1111/j.1432-1033.1978.tb12615.x. [DOI] [PubMed] [Google Scholar]
- Nohl H., Hegner D. Do mitochondria produce oxygen radicals in vivo? Eur J Biochem. 1978 Jan 16;82(2):563–567. doi: 10.1111/j.1432-1033.1978.tb12051.x. [DOI] [PubMed] [Google Scholar]
- Nohl H., Krämer R. Molecular basis of age-dependent changes in the activity of adenine nucleotide translocase. Mech Ageing Dev. 1980 Sep-Oct;14(1-2):137–144. doi: 10.1016/0047-6374(80)90112-8. [DOI] [PubMed] [Google Scholar]
- Penttilå A., Ahonen A. Electron microscopical and enzyme histochemical changes in the rat myocardium during prolonged autolysis. Beitr Pathol. 1976 Apr;157(2):126–141. doi: 10.1016/s0005-8165(76)80099-6. [DOI] [PubMed] [Google Scholar]
- Port S., Cobb F. R., Coleman R. E., Jones R. H. Effect of age on the response of the left ventricular ejection fraction to exercise. N Engl J Med. 1980 Nov 13;303(20):1133–1137. doi: 10.1056/NEJM198011133032001. [DOI] [PubMed] [Google Scholar]
- Sherratt H. S., Cartlidge N. E., Johnson M. A., Turnbull D. M. Mitochondrial myopathy with partial cytochrome oxidase deficiency and impaired oxidation of NADH-linked substrates. J Inherit Metab Dis. 1984;7 (Suppl 2):107–108. doi: 10.1007/978-94-009-5612-4_28. [DOI] [PubMed] [Google Scholar]
- Strehler B. L. Genetic instability as the primary cause of human aging. Exp Gerontol. 1986;21(4-5):283–319. doi: 10.1016/0531-5565(86)90038-0. [DOI] [PubMed] [Google Scholar]
- Turnbull D. M., Johnson M. A., Dick D. J., Cartlidge N. E., Sherratt H. S. Partial cytochrome oxidase deficiency without subsarcolemmal accumulation of mitochondria in chronic progressive external ophthalmoplegia. J Neurol Sci. 1985 Aug;70(1):93–100. doi: 10.1016/0022-510x(85)90191-1. [DOI] [PubMed] [Google Scholar]
- Van Biervliet J. P., Bruinvis L., Ketting D., De Bree P. K., Van der Heiden C., Wadman S. K. Hereditary mitochondrial myopathy with lactic acidemia, a De Toni-Fanconi-Debré syndrome, and a defective respiratory chain in voluntary striated muscles. Pediatr Res. 1977 Oct;11(10 Pt 2):1088–1093. doi: 10.1203/00006450-197711100-00005. [DOI] [PubMed] [Google Scholar]
- Vladimirov Y. A., Olenev V. I., Suslova T. B., Cheremisina Z. P. Lipid peroxidation in mitochondrial membrane. Adv Lipid Res. 1980;17:173–249. doi: 10.1016/b978-0-12-024917-6.50011-2. [DOI] [PubMed] [Google Scholar]
- Wilson P. D. Enzyme changes in ageing mammals. Gerontologia. 1973;19(2):79–125. doi: 10.1159/000211964. [DOI] [PubMed] [Google Scholar]
- da Silva P. T., Higuti I. H., Stencel M., de Paiva Campello A., do Nascimento A. J. Studies on rat liver mitochondria: 4. Enzyme activities in mitochondria preserved at 0-4 degrees C. Cell Biochem Funct. 1984 Jan;2(1):49–52. doi: 10.1002/cbf.290020113. [DOI] [PubMed] [Google Scholar]