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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. Cardiovascular Drugs and Therapy , 21 (6) pp. 467-469. 10.1007/s10557-007-6067-6.

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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<0.05) 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. © 2007 Springer Science+Business Media, LLC.

Type: Article
Title: The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore
DOI: 10.1007/s10557-007-6067-6
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/10029766
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