Monday, May 26, 2008

Arginase and ageing - rethinking SAM

Age-Related Alteration of Arginase Activity Impacts on Severity of Leishmaniasis
is a very exciting paper, so convincing in fact that it makes me question whether my hypothesis on SAM is of any use at all to explain susceptibility to leishmaniasis. Arginase activity has been shown time and time again to be crucial to parasite proliferation, but I always wondered whether there was some proverbial elephant standing in the room that no-one mentioned. The SAM story was meant to complement and expand the arginase part and I still believe that with its dual role in polyamine synthesis and regulation of gene expression amongst others, SAM might still be shown to play a role in this experimental system.

At first, I thought that by changes in DNA methylation SOCS expression would be altered affecting cell signalling and arginase activity in host macrophages. This may still be the case, but maybe it would be better to focus on the polyamine synthesis aspect at first. If antimony treatment should deplete SAM levels this could be investigated by incubating macrophage cultures with antimony and measure polyamine levels by thin layer chromatography as carried out by Modolell and colleagues.

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