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Increased susceptibility to Ca 2+ ‐induced permeability transition and to cytochrome c release in rat heart mitochondria with aging: effect of melatonin
Author(s) -
Petrosillo Giuseppe,
Moro Nicola,
Paradies Valeria,
Ruggiero Francesca M.,
Paradies Giuseppe
Publication year - 2010
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2010.00758.x
Subject(s) - cardiolipin , melatonin , mitochondrion , cytochrome c , mitochondrial permeability transition pore , endocrinology , medicine , biology , chemistry , apoptosis , programmed cell death , biochemistry , phospholipid , membrane
Aging is associated with a decline of cardiac function. The mitochondrial permeability transition (MPT) may be a factor in cardiac dysfunction associated with aging. We investigated the effect of aging and long‐term treatment with melatonin (approximately 10 mg/kg b.w./day for 2 months), a known natural antioxidant, on the susceptibility to Ca 2+ ‐induced MPT opening and cytochrome c release in rat heart mitochondria. The mitochondrial content of normal and oxidized cardiolipin as a function of aging and melatonin treatment was also analyzed. Mitochondria from aged rats (24 month old) displayed an increased susceptibility to Ca 2+ ‐induced MPT opening, associated with an elevated release of cytochrome c, when compared with young control animals (5 month old). Melatonin treatment counteracted both these processes. Aging was also associated with an oxidation/depletion of cardiolipin which could be counteracted as well by melatonin. It is proposed that the increased level of oxidized cardiolipin could be responsible, at least in part, for the increased susceptibility to Ca 2+ ‐induced MPT opening and cytochrome c release in rat heart mitochondria with aging. Melatonin treatment counteracts both these processes, most likely, by preventing the oxidation/depletion of cardiolipin. Our results might have implications in the necrotic and apoptotic myocytes cell death in aged myocardium, particularly in ischemia/reperfusion injury.