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Uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
- Title
- Uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
- Authors
- Choi J.W.; Yoo B.-K.; Shin C.Y.; Ryu M.-K.; Ryu J.H.; Kouni M.H.e.; Lee J.-C.; Kim W.-K.; Ko K.H.
- Ewha Authors
- 김원기
- SCOPUS Author ID
- 김원기
- Issue Date
- 2006
- Journal Title
- Neuroscience Research
- ISSN
- 0168-0102
- Citation
- Neuroscience Research vol. 56, no. 1, pp. 111 - 118
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- We previously reported that in immunostimulated astrocytes, glucose deprivation induced cell death via the loss of ATP, reduced glutathione, and mitochondrial transmembrane potential. The cytotoxicity was due to reactive nitrogen and oxygen species and blocked by adenosine, a purine nucleoside, via the preservation of cellular ATP. Here, we investigated whether uridine, a pyrimidine nucleoside, could prevent the glucose deprivation-induced cytotoxicity in LPS + IFN-γ-treated (immunostimulated) astrocytes. Glucose deprivation induced the death of immunostimulated cells, which was significantly reduced by uridine. Glucose deprivation rapidly decreased cellular ATP levels in immunostimulated astrocytes, which was also reversed by uridine. The inhibition of cellular uptake of uridine by S-(4-nitrobenzyl)-6-thioinosine attenuated the protective effect of uridine. mRNA and protein expression for uridine phosphorylase, an enzyme catalyzing reversible phosphorolysis of uridine, were observed in rat brain as well as primary astrocytes. 5-(Phenylthio)acyclouridine (PTAU), a specific inhibitor of uridine phosphorylase, inhibited the protective effect of uridine. Additionally, the loss of mitochondrial transmembrane potential and reduced glutathione by glucose deprivation in immunostimulated cells was attenuated by uridine, which was also reversed by PTAU. These results provide the first evidence that uridine protects immunostimulated astrocytes against the glucose deprivation-induced death by preserving intracellular ATP through the action of uridine phosphorylase. © 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society.
- DOI
- 10.1016/j.neures.2006.06.004
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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