ASMase inhibition

The lysosomal acid sphingomyelinase (aSMase) isoform is inhibited by L-camitine, a cofactor of acyl-coenzyme A transport in mitochondria (107, 108), and by phosphatidylinositol polyphosphates, which occur in plant, yeast, and mammalian cells (109). 

CD95-induced apoptosis in the human T-cell line Jurkat ean be readily inhibited by bloeking aSMase (A.Billich, unpublished data). 

To summarize, based on the available data, pharmacological inhibition of ASMase might be an opportunity to prevent apoptosis, in particular in the liver, without influencing T-cell apoptosis. In fact, hepatocyte apoptosis is an important element in a number of liver diseases, ranging from cholestatic and alcoholic liver disease to autoimmune and viral hepatitis (Eichhorst, 2005). Furthermore, a role of ASMase-produced ceramide in neuronal and myocardial apoptosis has been implicated from studies in models of rat cerebral and rabbit heart ischemia, respectively (Yu et al., 2000 Argaud et al., 2004) the criticism to the latter two studies is, however, that their conclusion rely on the use of the xanthogenate D609, which inhibits ASMase in an indirect way but certainly is not specific for that enzyme. 

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