Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis

Meifeng Xu, Yigang Wang, Kyoji Hirai, Ahmar Ayub, Muhammad Ashraf

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
StatePublished - Feb 1 2001
Externally publishedYes

Fingerprint

Permeability
Apoptosis
Calcium
Muscle Cells
Cyclosporine
Mitochondria
Atractyloside
ATP Translocases Mitochondrial ADP
Wounds and Injuries
Cytochromes c
Reperfusion Injury
L-Lactate Dehydrogenase
Cytoplasm
Cell Death
Electrons

Keywords

  • Anoxia-reoxygenation
  • Cytochrome c
  • Neonatal rat myocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis. / Xu, Meifeng; Wang, Yigang; Hirai, Kyoji; Ayub, Ahmar; Ashraf, Muhammad.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 2 49-2, 01.02.2001.

Research output: Contribution to journalArticle

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