Yoo Byoung-Kwon, Choi Ji Woong, Yoon Seo Young, Ko Kwang Ho
Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
Neurosci Res. 2005 Jan;51(1):39-44. doi: 10.1016/j.neures.2004.09.008.
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.
此前，我们已经表明，过氧化氢（H2O2）和葡萄糖剥夺（GD）可诱导星形胶质细胞中的ATP损失和细胞死亡。在此，我们报告称，腺苷及相关嘌呤核苷可恢复细胞内ATP水平，并完全防止在同时接受H2O2和葡萄糖剥夺处理的大鼠原代星形胶质细胞中发生细胞死亡。H2O2在时间和浓度依赖性上，诱导葡萄糖剥夺的星形胶质细胞发生细胞死亡和ATP损失。腺苷或ATP以剂量依赖性方式防止了由H2O2/GD引起的星形胶质细胞死亡和ATP损失。此外，用赤藓红-9-（-羟基-3-壬基）腺苷或S-（4-硝基苄基）-6-硫代肌苷抑制腺苷脱氨或转运，在很大程度上减弱了腺苷的保护作用。其他嘌呤核苷，如肌苷、鸟苷、ADP、AMP、ITP和GTP也显示出类似的保护作用。腺苷或ATP还可阻止H2O2处理的葡萄糖剥夺的星形胶质细胞中的线粒体功能障碍和谷胱甘肽（GSH）耗竭。目前的结果表明，腺苷及相关嘌呤核苷可能通过恢复细胞内ATP水平，保护星形胶质细胞免受H2O2和葡萄糖剥夺诱导的增强性死亡。
