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Adenosine and purine nucleosides protect rat primary astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death: Preservation of intracellular ATP level

Title
Adenosine and purine nucleosides protect rat primary astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death: Preservation of intracellular ATP level
Authors
Shin, CYJang, ESChoi, JWRyu, JRKim, WKKim, HCChoi, CRKo, KH
Ewha Authors
김원기
Issue Date
2002
Journal Title
EXPERIMENTAL NEUROLOGY
ISSN
0014-4886JCR Link
Citation
vol. 176, no. 1, pp. 175 - 182
Keywords
adenosineATPastrocyteperoxynitriteglucose-deprivation
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Previously we have reported that immunostimulated astrocytes became highly vulnerable to glucose deprivation. In the present study we examined the effect of various kinds of nucleosides on the augmented death of glucose-deprived immunostimulated astrocytes. Preincubation with interferon-gamma (100 U/ml) and lipopolysaccharide (1 mug/ml) for 48 h and continuous exposure to glucose deprivation (4 h) significantly induced the lactate dehydrogenase (LDH) release, as a marker of cell injury or death, from astrocytes. The glucose deprivation-induced augmented cell death in immunostimulated astrocytes was mimicked by exogenous peroxynitrite generator 3-morpholinosydnonimine (SIN-1). The increased death in immunostimulated or SIN-1-treated astrocytes deprived of glucose was blocked by adenosine and ATP. Other purine nucleos(t)ides, not pyrimidine nucleotides, also showed similar protective effects. Adenosine receptor agonist R(-)-N-(2-phenylisopropyl)-adenosine or N-cyclohexyladenosine did not alter the augmented cell death. Adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, xanthine amine congener or 3,7-dimethyl-1-propargylxanthine also did not reverse the protective effect of adenosine. Intracellular ATP levels rapidly decreased prior to the LDH release in glucose-deprived immunostimulated astrocytes. The loss of intracellular ATP was prevented by adenosine and other purine nucleotides. The present results suggest that adenosine and their metabolites may protect astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death by serving as substrates for intracellular ATP generation. (C) 2002 Elsevier Science (USA).
DOI
10.1006/exnr.2002.7913
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자연과학대학 > 화학·나노과학전공 > Journal papers
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