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The cardioprotective effect of necrostatin requires the cyclophilin-d component of the mitochondrial permeability transition pore

Lim, SY; Davidson, SM; Mocanu, MM; Yellon, DM; Smith, CCT; (2007) The cardioprotective effect of necrostatin requires the cyclophilin-d component of the mitochondrial permeability transition pore. CARDIOVASC DRUG THER , 21 (6) 467 - 469. 10.1007/s10557-007-6067-6. Gold open access

Abstract

Background Necrostatin (Nec-1) protects against ischemia-reperfusion (IR) injury in both brain and heart. We have previously reported in this journal that necrostatin can delay opening of the mitochondrial permeability transition pore (MPTP) in isolated cardiomyocytes.Aim The aim of the present study was to investigate in more detail the role played by the MPTP in necrostatin-mediated cardioprotection employing mice lacking a key component of the MPTP, namely cyclophilin-D.Method Anaesthetized wild type (WT) and cyclophilin-D knockout (Cyp-D-/-) mice underwent an open-chest procedure involving 30 min of myocardial ischemia and 2 h of reperfusion, with subsequent infarct size assessed by triphenyltetrazolium staining. Nec-1, given at reperfusion, significantly limited infarct size in WT mice (17.7 +/- 3% vs. 54.3 +/- 3%, P < Ce0.05) but not in Cyp-D-/- mice (28.3 +/- 7% vs. 30.8 +/- 6%, P > 0.05).Conclusion The data obtained in Cyp-D-/- mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.

Type:Article
Title:The cardioprotective effect of necrostatin requires the cyclophilin-d component of the mitochondrial permeability transition pore
Open access status:An open access publication
DOI:10.1007/s10557-007-6067-6
Publisher version:http://ukpmc.ac.uk/abstract/MED/17965927
Keywords:necrostatin, mitochondrial permeability transition pore, cyclophilin-D, CELL-DEATH, ISCHEMIA, REPERFUSION, INJURY
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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