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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2001-11-0073. This Article Full Text (PDF) All Versions of this Article: 2001-11-0073v1 100/5/1802    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Witkowski, J. M Articles by Hellmann, A. Search for Related Content PubMed PubMed Citation Articles by Witkowski, J. M Articles by Hellmann, A. Social Bookmarking                   What's this? Submitted November 27, 2001 Accepted April 13, 2002 Modulation of the activity of calcium-activated neutral proteases (calpains) in chronic lymphocytic leukemia (B-CLL) cells Jacek M Witkowski*, Emilia Zmuda-Trzebiatowska, Jakub Swiercz, Miroslawa Cichorek, Hanna Ciepluch, Krzysztof Lewandowski, Ewa Bryl, and Andrzej Hellmann Pathophysiology, Medical University of Gdansk, Gdansk, Poland Embryology, Medical University of Gdansk, Gdansk, Poland Hematology, Medical University of Gdansk, Gdansk, Poland Immunopathology, Medical University of Gdansk, Gdansk, Poland * Corresponding author; email: jawit{at}amedec.amg.gda.pl. Decreased susceptibility to apoptosis and impaired proliferative control are thought to be responsible for prolonged lifespan and accumulation of chronic lymphocytic leukemia (B-CLL) cells. The activity of calpains (calcium-dependent, neutral proteases, active in the cells responding to signals inducing a rise of cytoplasmic Ca2+) is involved in the regulation of apoptosis of some cell types by interaction with caspase-3. This work verifies the hypothesis of the abnormal activity of calpains and its role in reduced apoptosis of the B-CLL cells. Casein zymography, RT-PCR and western blotting were used for identification and quantification of the activity and expression of calpains in B-CLL cells and purified normal B-lymphocytes. The activity and expression of µ-calpain (requiring micromolar Ca2+ for activation) are significantly higher in the leukemic than in non-malignant cells. Contrarily, the activity and expression of m-calpain (requiring millimolar Ca2+) as well as the expression of calpastatin (an endogenous inhibitor of calpains) are unchanged or reduced in the B-CLL lymphocytes. Correspondingly, the activity of caspase-3 is many times lower in the B-CLL cells than in normal B-lymphocytes. Inhibition of overexpressed µ-calpain in living B-CLL cells in vitro results in doubling of the proportion of the cells undergoing spontaneous apoptosis. This observation suggests a possible role for calpains in longer survival of the B-CLL cells and may open new therapeutic possibilities. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Lyubchenko, J. P. Nielsen, S. M. Miller, G. A. Liubchenko, and V. M. Holers Role of initial protein phosphorylation events and localized release-activated calcium influx in B cell antigen receptor signaling J. Leukoc. Biol., February 1, 2009; 85(2): 298 - 309. [Abstract] [Full Text] [PDF] M. Niapour, Y. Yu, and S. A. 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