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Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model

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Abstract

The activation of the [Ca2+]-dependent cysteine protease calpain plays an important role in ischemic injury. Here, the levels of two calpain-specific substrates, p35 protein and eukaryotic initiation factor 4G (eIF4G), as well as its physiological regulator calpastatin, were investigated in a rat model of transient global cerebral ischemia with or without ischemic tolerance (IT). Extracts of the cerebral cortex, whole hippocampus and hippocampal subregions after 30 min of ischemia and different reperfusion times (30 min and 4 h) were used. In rats without IT, the p35 levels slightly decreased after ischemia or reperfusion, whereas the levels of p25 (the truncated form of p35) were much higher than those in sham control rats after ischemia and remained elevated during reperfusion. The eIF4G levels deeply diminished after reperfusion and the decrease was significantly greater in CA1 and the rest of the hippocampus than in the cortex. By contrast, the calpastatin levels did not significantly decrease during ischemia or early reperfusion, but were upregulated after 4 h of reperfusion in the cortex. Although IT did not promote significant changes in p35 and p25 levels, it induced a slight increase in calpastatin and eIF4G levels in the hippocampal subregions after 4 h of reperfusion.

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Acknowledgments

This work was supported by grants SPAIN-02/0304 and 05/0312 from the Ministerio de Sanidad y Consumo (FIS), and grants SK-VEGA 2/3219/23 and APVT 51-0219-04 from the Slovak Academy of Sciences. I. Ayuso, L. García-Bonilla and D. Piñeiro gratefully acknowledge fellowships from the FIS.

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Authors and Affiliations

  1. Servicio de Bioquímica, Departamento de Investigación, Hospital Ramón y Cajal, Ctra. Colmenar Km. 9, 28034, Madrid, Spain

    L. García-Bonilla, D. Piñeiro, I. Ayuso, M. Gómez-Calcerrada & M. Salinas

  2. Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, 04001 , Kosice, Slovak Republic

    J. Burda

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  1. L. García-Bonilla
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  2. J. Burda
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  6. M. Salinas
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Correspondence to M. Salinas.

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García-Bonilla, L., Burda, J., Piñeiro, D. et al. Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model. Neurochem Res 31, 1433–1441 (2006). https://doi.org/10.1007/s11064-006-9195-7

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  • DOI: https://doi.org/10.1007/s11064-006-9195-7

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