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

Balamurugan, Kuppusamy ; Rajaram, Rama ; Ramasami, Thirumalachari (2004) Caspase-3: Its potential involvement in Cr(III)-induced apoptosis of lymphocytes Molecular and Cellular Biochemistry, 259 (1-2). pp. 43-51. ISSN 0300-8177

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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.

Item Type:Article
Source:Copyright of this article belongs to Springer.
Keywords:Cr(III) Complexes; ROS; Src-family Tyrosine Kinases; Caspase-3; Apoptosis; Chromium Toxicity
ID Code:53344
Deposited On:10 Aug 2011 09:55
Last Modified:10 Aug 2011 09:55

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