Cleavage of the calpain inhibitor, calpastatin, during apoptosis (original) (raw)

Cell Death & Differentiation volume 5, pages 1028–1033 (1998)Cite this article

Abstract

Calpain activity is thought to be essential for the execution of apoptotic cell death in certain experimental models. In the present study, the physiological inhibitor of calpain, calpastatin, was found to be cleaved in three different apoptotic systems. The 110–120 kDa calpastatin protein of Jurkat T-lymphocytes and U937 monocytic leukemia cells was cleaved to a 65–70 kDa form after the induction of apoptosis with anti-CD95 monoclonal antibody, staurosporine or TNF. Cleavage of calpastatin in apoptotic cells occurred simultaneously with the cleavage of the DNA repair enzyme, poly(ADP-ribose) polymerase. The caspase inhibitors VAD-cmk and IETD-fmk prevented calpastatin cleavage in all three systems. Calpain inhibitor I, however, suppressed calpastatin cleavage only during TNF-induced apoptosis. Other protease inhibitors, such as lactacystin and pepstatin A, did not confer any significant protection against apoptotic calpastatin cleavage. The results from in vitro incubations with cell lysates and purified enzymes showed that calpain I, calpain II and recombinant caspase-3, all cleaved calpastatin, with varying efficiency. In conclusion, the results of the present study suggest that caspases may cleave calpastatin and thus, regulate calpain activity during apoptotic cell death.

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  1. Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet Box 210, Stockholm, S-17177, Sweden
    M Isabella Pörn-Ares, Afshin Samali & Sten Orrenius

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  1. M Isabella Pörn-Ares
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  2. Afshin Samali
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  3. Sten Orrenius
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Correspondence toM Isabella Pörn-Ares.

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Edited by G. Melino

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Pörn-Ares, M., Samali, A. & Orrenius, S. Cleavage of the calpain inhibitor, calpastatin, during apoptosis.Cell Death Differ 5, 1028–1033 (1998). https://doi.org/10.1038/sj.cdd.4400424

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