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Caspase-3: Its potential involvement in Cr(III)-induced apoptosis of lymphocytes

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Abstract

In this study, we have examined the role of caspase-3 in apoptosis of lymphocytes induced by the chromium(III) complexes viz. tris-(1,10-phenanthroline)chromium(III) chloride (Cr(III)-phen) and trans-diaqua[1,3-bis(salicylideneamino)propane-chromium(III)] perchlorate (Cr(III)-salprn). Evidence for caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in lymphocytes exposed to Cr(III) complexes is revealed through Western blotting analysis. Blocking the activity of caspase-3 with z-DEVD-fmk, prevents apoptosis as evidenced through [3H]-thymidine incorporation, DNA fragmentation assay and measurement of sub-G1 cells by flow cytometry. Pretreatment of lymphocytes with free radical scavengers completely attenuates the activity of caspase-3 suggesting that reactive oxygen species (ROS) are upstream activators of caspase-3. Preincubation of lymphocytes with PP2, a selective Src-family tyrosine kinase inhibitor, abolishes the activation of caspase-3 indicating that Src-family tyrosine kinases viz. p56lck, p59fyn and p53/56lyn are mediators of caspase-3 activation during Cr(III) exposure. Collectively, our findings support a plausible mechanism in which Cr(III) mediates ROS generation that precedes the up-regulation of p56lck, p59fyn and p53/56lyn which eventually activates caspase-3 to promote apoptotic cell death of lymphocytes. To our knowledge, this is the first report suggesting the importance of Src-family tyrosine kinases for the activation of caspase-3 in metal-induced apoptotic cell death.

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  1. Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, 600 020, India

    Kuppusamy Balamurugan, Rama Rajaram & Thirumalachari Ramasami

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  1. Kuppusamy Balamurugan
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  3. Thirumalachari Ramasami
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Balamurugan, K., Rajaram, R. & Ramasami, T. Caspase-3: Its potential involvement in Cr(III)-induced apoptosis of lymphocytes. Mol Cell Biochem 259, 43–51 (2004). https://doi.org/10.1023/B:MCBI.0000021343.54495.8c

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