AJP - Heart AJP: Renal Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (July 8, 2005). doi:10.1152/ajpheart.00165.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/5/H2153    most recent
00165.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (12)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gomez, L.
Right arrow Articles by Ovize, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gomez, L.
Right arrow Articles by Ovize, M.
Submitted on February 17, 2005
Accepted on June 21, 2005

Fas-independent Mitochondrial Damage Trigger Cardiomyocyte Death following Ischemia-Reperfusion

Ludovic Gomez1, Nicolas Chavanis2, Laurent Argaud2, Lara Chalabreysse2, Odile Gateau-Roesch1, Jean Ninet3, and Michel Ovize2*

1 Inserm E0226, Lyon, France
2 Inserm E0226, Lyon, France; Hospices Civils de Lyon, Lyon, France
3 Hospices Civils de Lyon, Lyon, France

* To whom correspondence should be addressed. E-mail: ovize{at}sante.univ-lyon1.fr.

The Fas/FasL ligand and mitochondria pathways have been involved in cell death in several cell types. We combined the genetic inactivation of the Fas receptor on one hand (lpr mice), to the pharmacological inhibition of the mitochondrial permeability transition pore (mPTP), on the other hand, to investigate which of these pathways is predominantly activated during prolonged ischemia-reperfusion. Anesthetized C57BL/6JICO (control) and C57BL/6-lpr mice were pretreated with either saline or cyclosporine A (40mg/kg, 3 times a day), an inhibitor of the mPTP, and underwent 25 minutes of ischemia and 24 hrs of reperfusion. After 24 hours of reperfusion, hearts were harvested: infarct size was assessed by TTC staining, myocardial apoptosis by caspase 3 activity and mitochondrial permeability transition by Ca2+-induced mPTP opening using a potentiometric approach. Infarct size was comparable in untreated control and lpr mice, ranging from 77 ± 5 % to 83 ±3 % of the area at risk. CsA significantly reduced infarct size in control and lpr hearts. Control and lpr hearts exhibited comparable increase in caspase 3 activity that averaged 57 ± 18 and 49 ± 5 pmol/min/mg, respectively. CsA treatment significantly reduced caspase 3 activity in control and lpr hearts. The Ca2+ overload required to open the mPTP was decreased to a similar extent in lpr and controls. CsA significantly attenuated Ca2+-induced mPTP opening in both groups. Our results suggest that the Fas pathway likely plays a minor role, whereas mitochondria are preferentially involved in mice cardiomyocyte death following a lethal ischemia-reperfusion injury.




This article has been cited by other articles:


Home page
 CirculationHome page
X. Zheng, D. Lian, A. Wong, M. Bygrave, T. E. Ichim, M. Khoshniat, X. Zhang, H. Sun, T. De Zordo, J. C. Lacefield, et al.
Novel Small Interfering RNA-Containing Solution Protecting Donor Organs in Heart Transplantation
Circulation, September 22, 2009; 120(12): 1099 - 1107.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
J. Xiao, Q. She, Y. Wang, K. Luo, Y. Yin, R. Hu, and K. Huang
Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction
Eur J Heart Fail, January 1, 2009; 11(1): 20 - 27.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
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]

Home page
 Cardiovasc ResHome page
D. Sanchis, M. Llovera, M. Ballester, and J. X. Comella
An alternative view of apoptosis in heart development and disease
Cardiovasc Res, February 1, 2008; 77(3): 448 - 451.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. Argaud, O. Gateau-Roesch, L. Augeul, E. Couture-Lepetit, J. Loufouat, L. Gomez, D. Robert, and M. Ovize
Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts
Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H386 - H391.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. Gomez, H. Thibault, A. Gharib, J.-M. Dumont, G. Vuagniaux, P. Scalfaro, G. Derumeaux, and M. Ovize
Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1654 - H1661.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. Thibault, L. Gomez, E. Donal, G. Pontier, M. Scherrer-Crosbie, M. Ovize, and G. Derumeaux
Acute myocardial infarction in mice: assessment of transmurality by strain rate imaging
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H496 - H502.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.