Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age.
There is a loss of myocytes in the aging heart due to necrosis and apoptosis. Oxidative stress, an apoptosis-inducing signal, may also increase in the aging heart. Cytosol and mitochondria isolated from the left and right ventricle of the hearts of 6-, 16-, and 24-mo-old male Fischer 344 rats were used to measure key markers of apoptosis and to assess oxidative stress. Cytosolic cytochrome c content was significantly elevated in the 16- and 24-mo-old animals compared with the 6-mo-old animals. Furthermore, Bcl-2, an antiapoptotic protein, showed a strong tendency to decrease with age, whereas Bax, a proapoptotic protein, remained unchanged. Apoptotic protease-activating factor 1 levels and caspase-3 activities were not different among the three age groups. Indicative of the chronic oxidative stress with age, heart mitochondria from old animals showed increases in manganese superoxide dismutase and glutathione peroxidase activity and increases in lipid peroxidation. This is the first study to report cytochrome c release from the mitochondria and alterations in Bcl-2 with age in vivo, providing a potential mechanism for the increase in apoptosis seen in the aging heart.
Phaneuf
Sharon
S
Biochemistry of Aging Laboratory, College of Health and Human Performance, Center for Exercise Science, College of Medicine, University of Florida, Gainesville, Florida 32611, USA.
Leeuwenburgh
Christiaan
C
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; C494828:Bax protein, rat; D003574:Cytochrome c Group; D005609:Free Radicals; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020169:Caspases