Sharon-1 - Cytochrome c release from mitochondria in the...

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Unformatted text preview: Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age SHARON PHANEUF AND CHRISTIAAN LEEUWENBURGH Biochemistry of Aging Laboratory, College of Health and Human Performance, Center for Exercise Science, College of Medicine, University of Florida, Gainesville, Florida 32611 Received 24 May 2001; accepted in final form 18 October 2001 Phaneuf, Sharon, and Christiaan Leeuwenburgh. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regulatory Integrative Comp Physiol 282: R423R430, 2002; 10.1152/ajpregu.00296.2001.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 cyto- chrome c content was significantly elevated in the 16- and 24-mo-old animals compared with the 6-mo-old animals. Fur- thermore, 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 oxida- tive stress with age, heart mitochondria from old animals showed increases in manganese superoxide dismutase and glutathione peroxidase activity and increases in lipid peroxi- dation. 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. apoptosome; free radicals; myocyte; Bcl-2 family; pro- grammed cell death AGING IS CHARACTERIZED BY a progressive deterioration in physiological functions and metabolic processes, ulti- mately leading to morbidity and mortality. In both humans and animals, the aging process in the heart has been associated with a decrease in the total num- ber of myocytes and reactive hypertrophy of the re- maining cells (2, 3, 28, 29). It is important to note that this cell loss occurs even in the absence of pathologies known to cause heart damage, such as atherosclerosis, diabetes, hypertension, and ischemic heart disease. For example, a healthy 70-yr-old male will have a 30% reduction in myocyte number strictly as a result of aging (28, 29). A reduction in the total number of myocytes may lead to an accelerated decline in cardiac functional capacity in the aged heart. In addition to cell loss via necrosis, apoptosis may be a major factor contributing to the loss of cardiac myocytes with age....
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Sharon-1 - Cytochrome c release from mitochondria in the...

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