Studies with a new cell line, derived from a cancerous tumor, reveal that normal responses to apoptotic signals to TNF-α are absent or significantly reduced when compared to normal cells from the same tissue. Further analysis reveals that the cells take up serine and palmitic acid when added to the culture media. Analysis of the levels of sphingosine show that they fluctuate with the same kinetics in both tumor-derived and normal cells. Which of the following sphingolipid metabolizing enzymes is most likely to be missing or significantly reduced in the tumor cells to explain the observations obtained?

Question

Quizplus · Accepted Answer

Ceramides play a role in apoptotic processes via the activation of the aspartate protease cathepsin D. Cathepsin D is associated with membranes and when activated by ceramides is released to the cytosol where it triggers the mitochondrial apoptosis pathway. Further evidence for the role of ceramides in negative growth responses is seen in cell cultures to which ceramide analogues are added. These types of assays demonstrate that ceramides induce oxidative stress, growth arrest, and apoptosis and/or necrosis. When derived from the sphingomyelins, ceramides are the products of the action of acid sphingomyelinase (ASMase). The importance of sphingomyelin as a source of ceramide can be evidenced by the fact that the activation of the ASAase pathway is a shared response to the effects of cytokines, stress, radiation, chemotherapeutic drugs, and pathogenic and cytotoxic agents. Several receptor- and non-receptor-mediated pathways, activated in response to stress such as those involving death ligands like TNF-α, are coupled to the activation of ASMase activity. The induction of ASMase in response to apoptotic triggers results in increased production of ceramides which then can initiate aspects of the apoptosis pathway.

Studies with a New Cell Line, Derived from a Cancerous