Eukaryotic translation initiation factor 4E is a cellular target for arsenic but not chromium toxicity.
Toxicologist 2005 Mar; 84(Suppl 1):238
The mRNA cap binding translation factor, eukaryotic translation initiation factor 4E (eIF4E), was studied as a potential cellular target for the toxicity and cell death induced by arsenic and chromium. Human cell lines HCT15, PLC/PR/5, HeLa and Chang, were treated with sodium arsenite (As) and potassium dichromate (Cr). Exposure to both As and Cr resulted in significant cytotoxicity and cell death in all four cell lines. In all the cell lines treated with As and Cr, the transcript for eIF4E did not exhibit any change compared with the corresponding control cells. However, in the cells treated with As alone, the cellular expression level of eIF4E protein was significantly lower compared to the corresponding control cells. Further studies revealed that exposure of cells to As, but not to Cr, resulted in significant induction of ubiquitination of eIF4E protein. Results of the experiments involving inhibitors for the cellular proteasome pathway confirmed that the exposure of As but not Cr activated the proteolysis of eIF4E mediated through the ubiquitin/proteasome pathway. Whether the As-induced cytotoxicity and cell death were due to the inhibition of eIF4E was studied by specifically silencing the expression of eIF4E gene using a small interfering RNA (SiRNA) targeting eIF4E gene expression. The SiRNA-mediated silencing of eIF4E gene resulted in cytotoxicity and cell death suggesting that eIF4E is a potential cellular target for cytotoxicity and cell death due to exposure to As.
Arsenic-compounds; Arsenites; Exposure-levels; Exposure-assessment; Cytotoxicity; Cytotoxic-effects; Cytotoxins; Cell-damage; Toxic-effects; Toxins; Chromium-compounds; Toxins
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana