Department of Neuroscience, Korea University College of Medicine, Seoul 136-705, Korea.
Exp Neurobiol. 2010 Sep;19(2):90-6. doi: 10.5607/en.2010.19.2.90. Epub 2010 Sep 30.
Previously, we reported that glucose-deprived astrocytes are more vulnerable to the cytotoxicity of peroxynitrite, the reaction product of nitric oxide and superoxide anion. The augmented vulnerability of glucose-deprived astrocytes to peroxynitrite cytotoxicity was dependent on their proliferation rate. Inhibition of cell cycle progression has been shown to inhibit the apoptotic cell death occurring in cerebral ischemia-reperfusion. In the present study, we demonstrate that the increased death of glucose-deprived astrocytes by peroxynitrte was largely blocked by the cell cycle phase G2/M transition blocker etoposide. However, the cytoprotective effect of etoposide was not associated with its inhibition of cell cycle progression. Instead, etoposide effectively scavenged peroxynitrite. However, etoposide did not scavenge individual nitric oxide and superoxide anion and it did not prevent the hydrogen peroxide-induced cytotoxicity. The present results indicate that etoposide prevents the toxicity of peroxynitrite in astrocytes by directly scavenging peroxynitrite, not by inhibiting cell cycle progression.
先前，我们报道过，在葡萄糖缺乏的情况下，星形胶质细胞对过氧亚硝酸盐（一氧化氮和超氧阴离子的反应产物）的细胞毒性更为敏感。葡萄糖缺乏的星形胶质细胞对过氧亚硝酸盐细胞毒性的易感性增加取决于它们的增殖率。已证明抑制细胞周期进程可抑制脑缺血再灌注过程中发生的凋亡性细胞死亡。在本研究中，我们证明，过氧亚硝酸盐引起的葡萄糖缺乏的星形胶质细胞死亡的增加在很大程度上被细胞周期 G2/M 期转换抑制剂依托泊苷所阻断。然而，依托泊苷的细胞保护作用与其抑制细胞周期进程无关。相反，依托泊苷能有效地清除过氧亚硝酸盐。然而，依托泊苷不能清除单个的一氧化氮和超氧阴离子，也不能防止过氧化氢引起的细胞毒性。本研究结果表明，依托泊苷通过直接清除过氧亚硝酸盐而不是通过抑制细胞周期进程来防止星形胶质细胞中的过氧亚硝酸盐毒性。
