8 January 2008 Calpain mediates AIF-regulated caspase-independent pathway in cisplatin-induced apoptosis
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Abstract
Mitochondrial apoptosis inducing factor (AIF) on activation can translocate to the nucleus and induce cell death via caspase-independent pathway in cisplatin-induced apoptosis. Yet the precise signal transduction pathway(s) which regulates AIF-induced apoptotic pathway still remains poorly understood. In this study, we investigated the molecular mechanism of AIF release and redistribution in cisplatin-induced apoptosis in living ASTC-a-1 cells, as assessed by real-time anlysis. Herein, We report that during cisplatin-induced apoptosis, calpain activation, as measured in intact cells by a fluorescent substrates, is an early event, taking place well before AIF release and caspase-3 activation. Confocal imaging of the cells transfected with AIF-GFP demonstrated that AIF release occurred about 9 h after cisplatin treatment. The event proceeded progressively over time, coinciding with a nuclear translocation and lasting for more than 2 hours. AIF release and redistribution were effectively inhibited in samples co-treated with calpeptin and PD150606, two selective calpain inhibitors. Therefore, our results clearly show the kinetics of AIF release and redistribution in cisplatin-induced apoptosis in living ASTC-a-1 cells, and calpain played a crucial role in these events.
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Lei Liu, Da Xing, Wei R. Chen, "Calpain mediates AIF-regulated caspase-independent pathway in cisplatin-induced apoptosis", Proc. SPIE 6826, Optics in Health Care and Biomedical Optics III, 68261R (8 January 2008); doi: 10.1117/12.760234; https://doi.org/10.1117/12.760234
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