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Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions

Balestri, Francesco and Giannecchini, Michela and Sgarrella, Francesco and Carta, Maria Caterina and Tozzi, Maria Grazia and Camici, Marcella (2007) Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions. Neurochemistry International, Vol. 50 (3), p. 517-523. ISSN 0197-0186. Article.

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DOI: 10.1016/j.neuint.2006.10.005


The brain depends on both glycolysis and mitochondrial oxidative phosphorylation for maintenance of ATP pools. Astrocytes play an integral role in brain functions providing trophic supports and energy substrates for neurons. In this paper, we report that human astrocytoma cells (ADF) undergoing ischemic conditions may use both purine and pyrimidine nucleosides as energy source to slow down cellular damage. The cells are subjected to metabolic stress conditions by exclusion of glucose and incubation with oligomycin (an inhibitor of oxidative phosphorylation). This treatment brings about a depletion of the ATP pool, with a concomitant increase in the AMP levels, which results in a significant decrease of the adenylate energy charge. The presence of purine nucleosides in the culture medium preserves the adenylate energy charge, and improves cell viability. Besides purine nucleosides, also pyrimidine nucleosides, such as uridine and, to a lesser extent, cytidine, are able to preserve the ATP pool. The determination of lactate in the incubation medium indicates that nucleosides can preserve the ATP pool through anaerobic glycolysis, thus pointing to a relevant role of the phosphorolytic cleavage of the N-glycosidic bond of nucleosides which generates, without energy expense, the phosphorylated pentose, which through the pentose phosphate pathway and glycolysis can be converted to energetic intermediates also in the absence of oxygen. In fact, ADF cells possess both purine nucleoside phosphorylase and uridine phosphorylase activities.

Item Type:Article
ID Code:7702
Uncontrolled Keywords:Neuroprotection, human astrocytoma, purine and pyrimidine nucleosides, oligomycin
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:Elsevier Science
Copyright Holders:© 2006 Elsevier Ltd.
Deposited On:14 Jun 2012 13:32

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