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Tumor necrosis factor-alpha participates in apoptosis in the limbic system after myocardial infarction

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Abstract

This study was designed to determine the role of tumor necrosis factor-alpha (TNFα) in apoptosis observed in the myocardium and limbic system after myocardial ischemia. PEG sTNFRI, a recombinant, human, soluble p55 Type 1 TNF receptor (3 mg/kg) or vehicle (saline) was administered s.c. to male Sprague-Dawley rats on days 5, 3 and 1 before myocardial ischemia. The animals were then subjected, under anesthesia, to left anterior descending coronary artery occlusion for 40 min, followed by 15-min or 72-h reperfusion. Caspase-3 and -8 activities as well as terminal dUTP nick-end labelling-positive cells were examined in the myocardium (subendocardial and subepicardial regions), lateral (LA) and medial amygdala (MA) and hippocampus (CA1, CA3, dentate gyrus (DG)). After 15 min of reperfusion, the subendocardial and CA1 regions presented an increase in caspase-3 activity, whereas caspase-8 activity appeared to be augmented in the DG. PEG sTNFRI inhibited caspase-8 activation in the DG. After 72 h of reperfusion, plasma TNFα levels were reduced in the treated groups. The DG, CA1, CA3 and MA showed an increment of caspase-8 activity, which was reversed by PEG sTNFRI, except in the MA. Furthermore, caspase-3 activity was increased in the CA1, DG, LA and MA. These results indicate that TNFα contributes to apoptosis via activation of the extrinsic pathway in the limbic system after myocardial infarction, which is not the case in the myocardium.

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Acknowledgments

The authors thank Pierre Fortier and Caroline Bouchard for their skillful assistance and technical expertise. They also thank Amgen for generously providing PEG sTNFRI. G.R. is a scholar of “Fonds de la recherche en santé du Québec” (FRSQ). S.K. and T.M.B. hold studentships from the FRSQ. This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC). The editorial assistance of Ovid Da Silva is acknowledged.

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Authors and Affiliations

  1. Département de pharmacologie, Université de Montréal, Québec, Canada

    S. Kaloustian, I. Rondeau, L. Lada-Moldovan & G. Rousseau

  2. Département de psychiatrie, Université de Montréal, Québec, Canada

    R. Godbout

  3. Centre de biomédecine, Hôpital du Sacré-Coeur de Montréal, 5400 boul, Gouin Ouest, Montréal, Québec, H4J 1C5, Canada

    S. Kaloustian, T. M. Bah, I. Rondeau, S. Mathieu, L. Lada-Moldovan, R. Godbout & G. Rousseau

  4. Département de Neurologie Fonctionnelle et Épileptologie, Hospices Civils de Lyon et Université Claude Bernard Lyon 1, Lyon, France

    S. Kaloustian & P. Ryvlin

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  1. S. Kaloustian
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  2. T. M. Bah
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  3. I. Rondeau
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  4. S. Mathieu
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  5. L. Lada-Moldovan
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Correspondence to G. Rousseau.

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Kaloustian, S., Bah, T.M., Rondeau, I. et al. Tumor necrosis factor-alpha participates in apoptosis in the limbic system after myocardial infarction. Apoptosis 14, 1308–1316 (2009). https://doi.org/10.1007/s10495-009-0395-x

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