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Synergetic Effects of Caspase 3 and μ-Calpain in XIAP-Breakdown upon Focal Cerebral Ischemia

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Abstract

Dysregulation of apoptosis is involved in a wide spectrum of disease ranging from proliferative to neurodegenerative disorders. The recently discovered X-linked inhibitor of apoptosis protein (XIAP) is among the most potent inhibitors of apoptosis. This protein binds to and inhibits both initiator caspases and effector caspases such as caspase-3. The aim of this study was to investigate the relationships between XIAP-breakdown, caspase activation in the development of delayed infarct upon ischemia. We demonstrated that endogenous XIAP is cleaved at least into two fragments during reperfusion following the ischemic insult. The two fragments produced seem to be related to caspase-3 and μ-calpain activities, which are massively enhanced in tissues challenged by ischemia. Therefore, degradation of XIAP by μ-calpain in our system may decrease the activation threshold of caspase-3 normally held in check by the IAPs and/or lead to auto-activation of other caspases.

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Acknowledgments

We thank Professor J. Stehle for scientific support. We are very grateful to A. Langhagen for technical support. Research performed in this laboratory on the roles of IAPs in apoptosis and cerebral ischemia was supported in part by the “Dr. Paul und Cilli Weill-Stiftung (Grant 8598924- to Dr. A. Rami)”.

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  1. Institute of Cellular and Molecular Anatomy, Dr. Senckenbergische Anatomie, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Abdelhaq Rami, Rachna Agarwal & Alexander Spahn

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  1. Abdelhaq Rami
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  2. Rachna Agarwal
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  3. Alexander Spahn
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Correspondence to Abdelhaq Rami.

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Special issue in honor of Naren Banik.

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Rami, A., Agarwal, R. & Spahn, A. Synergetic Effects of Caspase 3 and μ-Calpain in XIAP-Breakdown upon Focal Cerebral Ischemia. Neurochem Res 32, 2072–2079 (2007). https://doi.org/10.1007/s11064-007-9361-6

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