Uptake and utilization of nucleosides for energy repletion

In this paper, we report that cells undergoing metabolic stress conditions may use the ribose moiety of nucleosides as energy source to slow down cellular damage. In fact, the phosphorolytic cleavage of the N-glycosidic bond of nucleosides generates, without energy expense, the phosphorylated pentose, which through pentose phosphate pathway and glycolysis, can be converted to energetic intermediates. In this respect, nucleosides may be considered as energy source, alternative or supplementary to glucose, which may become of primary importance especially in conditions of cellular stress. In accordance with the role of these compounds in energy repletion, we also show that the uptake of nucleosides is increased when the energetic demand of the cell is enhanced. As cell model, we have used a human colon carcinoma cell line, LoVo, and the depletion of ATP, with a concomitant fall in the cell energy charge, has been induced by exclusion of glucose from the medium and pre-incubation with oligomycin, an inhibitor of oxidative phosphorylation. In these conditions of energy starvation, we show that the uptake of 2'-deoxyadenosine in LoVo cells is significantly enhanced, and that the phosphorylated ribose moiety of inosine can be used for energy repletion through anaerobic glycolysis. Our data support previous reports indicating that the phosphorylated ribose stemming from the intracellular catabolism of nucleosides may be used in eukaryots as energy source, and advance our knowledge on the regulation of the uptake of nucleosides in eukaryotic cells.