Abstract
We tested the hypothesis whether calcium preconditioning (CPC) reduces reoxygenation injury by inhibiting mitochondrial permeability transition (MPT). Cultured myocytes were preconditioned by a brief exposure to 1.5 mM calcium (CPC) and subjected to 3 h of anoxia followed by 2 h of reoxygenation (A-R). Myocytes were also treated with 0.2 μM/1 cyclosporin A (CsA), an inhibitor of MPT, before A-R. A significant increase of viable cells and reduced lactate dehydrogenase release was observed both in CPC- and CsA-treated myocytes compared with the A-R group. Cytochrome c release was predominantly observed in the cytoplasm of myocytes in the A-R group in contrast with CPC- or CsA-treated groups, where it was restricted only to mitochondria. Similarly, the cell death by apoptosis was also markedly attenuated in these groups. Electron-dense Ca2+ deposits in mitochondria were also less frequent. Atractyloside (20 μM/l), an adenine nucleotide translocase inhibitor, caused changes similar to those in the A-R group, suggesting a role of MPT in A-R injury. Protection by inhibition of MPT by CsA and CPC suggests that MPT plays an important role in reoxygenation/ reperfusion injury. The data further suggest that preconditioning inhibits MPT by inhibiting Ca2+ accumulation by mitochondria.
Original language | English (US) |
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Pages (from-to) | H899-H908 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 280 |
Issue number | 2 49-2 |
DOIs | |
State | Published - Feb 2001 |
Externally published | Yes |
Keywords
- Anoxia-reoxygenation
- Cytochrome c
- Neonatal rat myocytes
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)