741B Poster - 12. Physiology, metabolism and aging
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Pavla Nedbalová; Lenka Chodáková; Nikol Kaislerová; Tomáš Doležal

Affiliation: University of South Bohemia in České Budějovice

Keywords:
b. metabolism; a. cellular immunity

Immune system activation is an energy demanding process requiring metabolic changes on the organismal level to ensure enough energy for immune cells to successfully face the pathogen. Our laboratory is interested in immunometabolism and uses Drosophila melanogaster larvae infected with parasitoid wasp Leptopilina boulardi to induce immune system activation and examine both, systemic metabolic changes caused by activated immunity and also metabolism changes of the immune cells themselves.
We have shown that larval immune cells actively produce extracellular adenosine as a systemic metabolism regulator upon infection. Extracellular adenosine is inhibiting glucose uptake by non-immune tissues such as imaginal discs. Thus, there is a high level of glucose available for activated hemocytes. The question is, what is the metabolic origin of this extracellular adenosine in hemocytes?
It is known in mammals that S-adenosylmethionine (SAM) cycle accelerates in activated immune cells. This metabolic pathway is responsible for the methylation of diverse biomolecules and this reaction produces S-adenosylhomocysteine (SAH), a potent inhibitor of this pathway, which is immediately converted to adenosine and homocysteine by S-adenosylhomocysteine hydrolase (Ahcy). Therefore, we have considered Ahcy and SAM cycle as a possible source of extracellular adenosine and we have already obtained data confirming this hypothesis and showing that SAM cycle activity increases also in activated D. melanogaster hemocytes.
Our data further imply that adenosine is not only released from hemocytes but is also highly used intracellularly. The first step of the SAM cycle is a unique reaction in which the adenosyl moiety of ATP is consumed along with methionine to synthesize SAM. We propose that a part of the adenosine pool produced by Ahcy is recycled back to ATP through the cooperation of adenosine kinase, adenylate kinase, and glycolysis, as losing all of the adenosine would be a huge energy wasting since all used ATP would have to be refilled by de novo purine synthesis. Our current effort is to examine this complex metabolic network showing adenosine as a crucial molecule affecting not only systemic energetic metabolism and supporting immune response but also participating in the intracellular energy balance of activated immune cells.