Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis

  • Authors:
    • Kenyon G. Daniel
    • Johnathan S. Anderson
    • Qing Zhong
    • Aslamuzzaman Kazi
    • Puja Gupta
    • Q. Ping Dou
  • View Affiliations

  • Published online on: August 1, 2003     https://doi.org/10.3892/ijmm.12.2.247
  • Pages: 247-252
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Abstract

Various stimuli including anticancer drugs are capable of initiating the apoptotic death program in human tumor cells via activation of caspases. Mitochondria play an essential role for cell apoptotic commitment. Previous studies have shown a potential role of calpain activation in apoptosis, however, the involved molecular mechanisms remain to be defined. In the current study, we have examined the expression and activation of mitochondrial calpain in Jurkat T leukemia cells, MCF-7 breast carcinoma and LNCaP prostate cancer cells during apoptosis induced by an anticancer drug (VP-16, tamoxifen) or the specific p38 kinase inhibitor PD-169316. Our results suggest that increased expression and autolysis of the mitochondrial calpain small subunit are tightly associated with calpain activation in an early stage of apoptosis. In contrast, there were no correlations observed between the early calpain activation and changes in levels of mitochondrial calpain large subunit and the endogenous calpain inhibitor calpastatin. Furthermore, pretreatment with the specific pharmacological calpain inhibitor calpeptin blocked the drug-induced calpain small subunit autolysis and calpain activation in mitochondria and inhibited apoptosis-associated caspase-3 activation, demonstrating that mitochondrial calpain activation through small subunit cleavage is an essential step for inducing tumor cell apoptosis by various anticancer drugs.

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August 2003
Volume 12 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Daniel KG, Anderson JS, Zhong Q, Kazi A, Gupta P and Dou QP: Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis. Int J Mol Med 12: 247-252, 2003
APA
Daniel, K.G., Anderson, J.S., Zhong, Q., Kazi, A., Gupta, P., & Dou, Q.P. (2003). Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis. International Journal of Molecular Medicine, 12, 247-252. https://doi.org/10.3892/ijmm.12.2.247
MLA
Daniel, K. G., Anderson, J. S., Zhong, Q., Kazi, A., Gupta, P., Dou, Q. P."Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis". International Journal of Molecular Medicine 12.2 (2003): 247-252.
Chicago
Daniel, K. G., Anderson, J. S., Zhong, Q., Kazi, A., Gupta, P., Dou, Q. P."Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis". International Journal of Molecular Medicine 12, no. 2 (2003): 247-252. https://doi.org/10.3892/ijmm.12.2.247