Ceramide Does Not Mediate TNF Toxicity in Rat Hepatoma Cells

Background: We have previously demonstrated that, in HTC cells, TNF toxicity requires a functional lysosomal compartment. We further investigated the pathways of TNF toxicity in these cells by focusing on wheter ceramide, which can be generated in lysosomes, mediates TNF toxicity. Methods: HTC cells were treated with ceramide or TNF; cell death measurerd by the Annexin-V/PI technique. Results and conclusions: HTC cells are killed by ceramide, and desipramine attenuates TNF toxicity but altered the lysosomal compartment. However, Bcl-2 ectopic expression or Bcl-xL upregulation by dexamethasone significantly protected from ceramide yet, did not prevent TNF toxicity. These results indicate that ceramide, though able to kill HTC cells, does not account for TNF toxicity in these cells.