Protective effect of adenosine and purine nucleos(t)ides against the death by hydrogen peroxide and glucose deprivation in rat primary astrocytes.
Previously, we have shown that hydrogen peroxide (H2O2) and glucose deprivation (GD) induced ATP loss and cell death in astrocytes. Here, we reported that adenosine and related purine nucleos(t)ides recovered cellular ATP level and completely prevented the cell death in rat primary astrocytes co-treated with H2O2 and glucose deprivation. Time- and concentration-dependently, H2O2 induced cell death and ATP loss in glucose-deprived astrocytes. Adenosine or ATP prevented both astrocytic death and ATP loss caused by H2O2/GD in dose-dependent manner. Further, inhibition of adenosine deamination or transport with erythro-9-(-hydroxy-3-nonyl)adenosine or S-(4-nitrobenzyl)-6-thioinosine largely attenuated the protective effect of adenosine. Other purine nucleos(t)ides such as inosine, guanosine, ADP, AMP, ITP and GTP also showed similar protective effects. Adenosine or ATP also blocked the mitochondrial dysfunction and glutathione (GSH) depletion in H2O2-treated glucose-deprived astrocytes. The present results suggest that adenosine and related purine nucleos(t)ides may protect astrocytes from H2O2 and glucose deprivation induced the potentiated death by restoration of cellular ATP level.
Yoo
Byoung-Kwon
BK
Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Choi
Ji Woong
JW
Yoon
Seo Young
SY
Ko
Kwang Ho
KH
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001562:Benzimidazoles / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000172:deficiency*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D001562:Benzimidazoles; D002232:Carbocyanines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D014970:Xanthines; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; C057837:3,7-dimethyl-1-propargylxanthine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C001789:4-nitrobenzylthioinosine; D005947:Glucose; D000225:Adenine; D000241:Adenosine; D013805:Theobromine; C030985:purine