© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Preconditioning delays Ca2+-induced mitochondrial permeability transition
aINSERM E0226, Laboratoire de Physiologie Lyon-Nord, Université Claude Bernard Lyon I, 8, Avenue Rockefeller, 69373 Lyon, France
bLaboratoire d'Anatomie Pathologique, Hôpital Louis Pradel, Lyon, France
cDépartement d'Urgence et de Réanimation Médicale, Hôpital Edouard Herriot, Lyon, France
* Corresponding author. Tel.: +33-4-7877-7074; fax: +33-4-7877-7175. laurent.argaud{at}chu-lyon.fr, ovize{at}rockefeller.univ-lyon1.fr
Objective: We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeability transition (MPT) pore opening. Methods: In protocol 1, New Zealand White rabbits underwent either no intervention (sham group) or 10 min of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control) by one episode of 5 min of ischemia and 5 min of reperfusion. Rabbits were pretreated by either saline or the MPT pore inhibitor cyclosporin A (CsA), or its non-immunosuppressive derivative Cs29 (10 mg/kg, IV bolus). Hearts were harvested and mitochondria isolated for further assessment of Ca2+-induced MPT using a Ca2+-sensitive micro-electrode. In protocol 2, C and PC hearts underwent 30 min of ischemia and 4 h of reperfusion. They were pretreated either by saline, CsA or Cs29, as in protocol 1. Infarct size was assessed by triphenyltetrazolium, and apoptosis by TUNEL staining. Results: In protocol 1, the Ca2+ overload required to induce MPT pore opening was significantly higher in PC than in C hearts. CsA and Cs29 significantly increased the Ca2+ overload required for MPT pore opening. In protocol 2, mean infarct size averaged 25% of the risk region in CsA/Cs29 treated hearts versus 15% in PC and 55% in controls (P<0.05 vs. C, P = ns vs. PC). Cardiomyocyte apoptosis was significantly reduced by PC and cyclosporin treatment with a mean apoptotic index of less than 2% in either group versus more than 11% in controls. Conclusion: This suggests that delayed opening of MPT pore may play a major role in ischemic PC.
KEYWORDS Preconditioning; Calcium (cellular); Mitochondria; Apoptosis; Necrosis
Time for primary review 22 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Gomez, B. Li, N. Mewton, I. Sanchez, C. Piot, M. Elbaz, and M. Ovize Inhibition of mitochondrial permeability transition pore opening: translation to patients Cardiovasc Res, July 15, 2009; 83(2): 226 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Paris, C. Perez-Pastene, E. Couve, P. Caviedes, S. LeDoux, and J. Segura-Aguilar Copper{middle dot}Dopamine Complex Induces Mitochondrial Autophagy Preceding Caspase-independent Apoptotic Cell Death J. Biol. Chem., May 15, 2009; 284(20): 13306 - 13315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Yocum, J. G. Gaudet, S. S. Lee, Y. Stern, L. A. Teverbaugh, R. R. Sciacca, C. W. Emala, D. O. Quest, P. C. McCormick, J. F. McKinsey, et al. Inducible Nitric Oxide Synthase Promoter Polymorphism Affords Protection Against Cognitive Dysfunction After Carotid Endarterectomy Stroke, May 1, 2009; 40(5): 1597 - 1603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. West, G. Rokosh, D. Obal, M. Velayutham, Y.-T. Xuan, B. G. Hill, R. J. Keith, J. Schrader, Y. Guo, D. J. Conklin, et al. Cardiac Myocyte-Specific Expression of Inducible Nitric Oxide Synthase Protects Against Ischemia/Reperfusion Injury by Preventing Mitochondrial Permeability Transition Circulation, November 4, 2008; 118(19): 1970 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. McAllister, H. Ashrafpour, N. Cahoon, N. Huang, M. A. Moses, P. C. Neligan, C. R. Forrest, J. E. Lipa, and C. Y. Pang Postconditioning for salvage of ischemic skeletal muscle from reperfusion injury: efficacy and mechanism Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R681 - R689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. T. Costa and K. D. Garlid Intramitochondrial signaling: interactions among mitoKATP, PKC{varepsilon}, ROS, and MPT Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H874 - H882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Piot, P. Croisille, P. Staat, H. Thibault, G. Rioufol, N. Mewton, R. Elbelghiti, T. T. Cung, E. Bonnefoy, D. Angoulvant, et al. Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction N. Engl. J. Med., July 31, 2008; 359(5): 473 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. N. Obame, C. Plin-Mercier, R. Assaly, R. Zini, J. L. Dubois-Rande, A. Berdeaux, and D. Morin Cardioprotective Effect of Morphine and a Blocker of Glycogen Synthase Kinase 3{beta}, SB216763 [3-(2,4-Dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via Inhibition of the Mitochondrial Permeability Transition Pore J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 252 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gomez, M. Paillard, H. Thibault, G. Derumeaux, and M. Ovize Inhibition of GSK3{beta} by Postconditioning Is Required to Prevent Opening of the Mitochondrial Permeability Transition Pore During Reperfusion Circulation, May 27, 2008; 117(21): 2761 - 2768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Clarke, I. Khaliulin, M. Das, J. E. Parker, K. J. Heesom, and A. P. Halestrap Inhibition of Mitochondrial Permeability Transition Pore Opening by Ischemic Preconditioning Is Probably Mediated by Reduction of Oxidative Stress Rather Than Mitochondrial Protein Phosphorylation Circ. Res., May 9, 2008; 102(9): 1082 - 1090. [Abstract] [Full Text] [PDF]
|
|