Uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase

Ji Woong Choi, Byoung Kwon Yoo, Chan Young Shin, Mi Kyoung Ryu, Jong Hoon Ryu, Mahmoud H.el Kouni, Jae Chul Lee, Won Ki Kim, Kwang Ho Ko

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalNeuroscience Research
Volume56
Issue number1
DOIs
Publication statusPublished - 2006 Sep

Keywords

  • ATP
  • Glucose deprivation
  • Immunostimulated
  • PTAU
  • Rat primary astrocyte
  • Uridine
  • Uridine phosphorylase

ASJC Scopus subject areas

  • Neuroscience(all)

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