© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo
aCardiovascular Research Institute, Department of Medicine (Cardiology Division), University of California, San Francisco, CA, USA
bReproductive Endocrinology Center, University of California, San Francisco, CA, USA
* Corresponding author. Service de Cardiologie B, Hôpital Arnaud de Villeneuve, 371, av Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Tel.: +33-046-733-6187; fax: +33-046-733-6186 c-piot{at}chu-montpellier.fr
Recently, we have demonstrated that ischemic preconditioning (IP) both limits infarct size and decreases internucleosomal DNA fragmentation in rat hearts in vivo, and that there was a direct correlation between myocardial infarct size and DNA fragmentation even after IP. In this study, we examined the ability of IP to attenuate processing and activation of caspase-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP), after prolonged ischemia and reperfusion using the same in vivo animal model. Rats that underwent IP and controls (Ctrl) were subjected to 30 min of left coronary artery occlusion followed by 180 min of reperfusion. IP was accomplished by five 5-min cycles of ischemia, each followed by 5 min of reperfusion. The amount of soluble nucleosomes was measured by enzyme-linked immunosorbent assay. Cleavage of caspases-1 and -3, and of one of their substrates PARP, was analyzed by Western blotting. Nucleosomal DNA fragmentation was significantly reduced in ischemic left ventricular (LV) tissue obtained from IP compared with Ctrl animals. The proforms of caspases-1 and -3, and the active form of PARP were not cleaved in the nonischemic LV region of both IP and Ctrl hearts. In contrast, the proform of caspase-3 and the active form of PARP were cleaved in the ischemic LV region of Ctrl hearts, while processing of caspase-1 was increased. Cleavages of caspases-1 and -3, and inactivation of PARP were prevented by IP. The results of this study indicate that IP attenuates both internucleosomal DNA fragmentation and caspases processing, and suggest that the prevention of caspases activation by IP may be important steps in protecting the heart against ischemia/reperfusion injury in vivo.
KEYWORDS Apoptosis; Ischemia; Reperfusion; Preconditioning
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
C. Pavoine and F. Pecker Sphingomyelinases: their regulation and roles in cardiovascular pathophysiology Cardiovasc Res, May 1, 2009; 82(2): 175 - 183. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Zhang, T. S. Park, and J. M. Gidday Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2573 - H2581. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Boodhwani, J. Feng, S. Mieno, B. Ramlawi, N. Sodha, R. Clements, and F. W. Sellke Effects of purified poloxamer 407 gel on vascular occlusion and the coronary endothelium. Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 736 - 741. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. M. Syed, H. S. Hahn, A. Odley, Y. Guo, J. G. Vallejo, R. A. Lynch, D. L. Mann, R. Bolli, and G. W. Dorn II Proapoptotic Effects of Caspase-1/Interleukin-Converting Enzyme Dominate in Myocardial Ischemia Circ. Res., May 27, 2005; 96(10): 1103 - 1109. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Barrere-Lemaire, N. Combes, C. Sportouch-Dukhan, S. Richard, J. Nargeot, and C. Piot Morphine mimics the antiapoptotic effect of preconditioning via an Ins(1,4,5)P3 signaling pathway in rat ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H83 - H88. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Okubo, Y. Tanabe, K. Takeda, M. Kitayama, S. Kanemitsu, R. C. Kukreja, and N. Takekoshi Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of {delta}-opioid receptor Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1786 - H1791. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Argaud, A.-F. Prigent, L. Chalabreysse, J. Loufouat, M. Lagarde, and M. Ovize Ceramide in the antiapoptotic effect of ischemic preconditioning Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H246 - H251. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z.-K. Wu, J. Laurikka, A. Saraste, V. Kyto, E. J. Pehkonen, T. Savunen, and M. R. Tarkka Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations Ann. Thorac. Surg., August 1, 2003; 76(2): 528 - 534. [Abstract] [Full Text] [PDF] |
||||
![]() |
P A J Krijnen, R Nijmeijer, C J L M Meijer, C A Visser, C E Hack, and H W M Niessen Apoptosis in myocardial ischaemia and infarction J. Clin. Pathol., November 1, 2002; 55(11): 801 - 811. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Zhang, D. M. Rosenbaum, A. R. Shaikh, Q. Li, P. S. Rosenbaum, D. J. Pelham, and S. Roth Ischemic Preconditioning Attenuates Apoptotic Cell Death in the Rat Retina Invest. Ophthalmol. Vis. Sci., September 1, 2002; 43(9): 3059 - 3066. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z.-Q. Zhao and J. Vinten-Johansen Myocardial apoptosis and ischemic preconditioning Cardiovasc Res, August 15, 2002; 55(3): 438 - 455. [Abstract] [Full Text] [PDF] |
||||
![]() |
C A Dinarello Novel targets for interleukin 18 binding protein Ann Rheum Dis, November 1, 2001; 60(90003): iii18 - 24. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Pomerantz, L. L. Reznikov, A. H. Harken, and C. A. Dinarello Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1beta PNAS, February 27, 2001; 98(5): 2871 - 2876. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Xu, Y. Wang, K. Hirai, A. Ayub, and M. Ashraf Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H899 - H908. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. O'Rourke Myocardial KATP Channels in Preconditioning Circ. Res., November 10, 2000; 87(10): 845 - 855. [Abstract] [Full Text] [PDF] |
||||









