title: Adenosine and purine nucleosides protect rat primary astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death: preservation of intracellular ATP level.
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 microg/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.
authors.affiliation: Department of Pharmacology, Seoul National University, Seoul, Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Jang
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Jae Ryun
authors.initials: JR
authors.lastname: Ryu
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Chang-Rak
authors.initials: CR
authors.lastname: Choi
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D020030:Nitric Oxide Donors / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000633:toxicity*; D011684:Purine Nucleosides / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020030:Nitric Oxide Donors; D011684:Purine Nucleosides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D030421:Peroxynitrous Acid; C002385:linsidomine; D000255:Adenosine Triphosphate; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D000241:Adenosine