The present study was designed to demonstrate the loss of ERK dependence on amplified apoptotic signals in arsenic treated rat hepatocytes. Arsenic trioxide treatment (10 μM) exhibited simultaneous activation of caspase 9, caspase 3 and caspase 8. Moreover, expression and secretion of Fas ligand was also prominent. Reduction in nuclear translocation of pERK was directly associated with caspase activation. Treatment with ERK inhibitor further augmented caspase activation. An experiment with Fas receptor blocked cells confirmed self amplification of apoptotic signals via Fas R/caspase 8 interaction.
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This work was supported by Department of Science & Technology (DST), Ministry of Science & Technology Project No SR/SO/AS-22/2008) and the National Academy of Sciences, India (NASI). AR is grateful to CSIR for a SRF, SC gratefully acknowledges DST for a SRF, SM is grateful to University Grants Commission for SRF and SB acknowledges NASI for the award of Senior Scientist Platinum Jubilee Fellowship.
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Ray, A., Chatterjee, S., Mukherjee, S. et al. Interplay of Loss of ERK Dependence and Amplification of Apoptotic Signals in Arsenic Treated Rat Hepatocytes. Natl. Acad. Sci. Lett. 36, 599–602 (2013). https://doi.org/10.1007/s40009-013-0175-6