Summary
Calpains are non-lysosomal, cysteine proteases ubiquitously expressed in animal cells. Most cells also express an inhibitor protein, calpastatin, that is highly specific for calpains. Among many proposed functions, calpains are thought to participate in apoptosis signaling through various pathways. Most studies of calpain function in apoptosis have relied on methodologies that cannot separate the influence of the conventional calpains (μ- and m-calpains) from other calpain family members, or non-calpain proteases in some cases. The present investigation addresses this issue by unambiguously altering the abundance of conventional calpains in cultured cells, and determining the effect on various models of apoptosis. Overexpression of μ-calpain enhanced apoptosis of Chinese hamster ovary (CHO) cells in response to the calcium ionophore A23187, the sarcolemma Ca2+-pump inhibitor, thapsigargin, or serum deprivation. Overexpression of calpastatin had the opposite effect. Altered expression of calpain or calpastatin had no detectable influence on apoptosis caused by expo-sure to H2O2, ultraviolet light, or the protein kinase inhibitor, staurosporine. Increased expression of μ-calpain protected against TNF-alpha triggered apoptosis. These results demonstrate that calpain/calpastatin balance is important in some forms of apoptosis in CHO cells, but not in others. Moreover, in the TNF-alpha apoptosis pathway calpains had a protective effect, as previously proposed (Han, Y., et al., 1999).
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Mellgren, R.L., Lu, T., Xu, Y. (2003). Altered Expression of Conventional Calpains Influences Apoptosis. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_29
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DOI: https://doi.org/10.1007/978-1-4615-0347-7_29
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