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


OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
The data obtained in Cyp-D-/- mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.
Lim
S Y
SY
The Hatter Cardiovascular Institute, University College London Hospital and Medical School, 67 Chenies Mews, London, WC1E 6HX, UK.
Davidson
S M
SM
Mocanu
M M
MM
Yellon
D M
DM
Smith
C C T
CC
D000818:Animals; D021983:Cyclophilins / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D000097322:Peptidyl-Prolyl Isomerase D
D021983:Cyclophilins; D007093:Imidazoles; D007211:Indoles; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C507699:necrostatin-1; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D