Nakamura Y, Yasuda M, Fujimori H, Kiyono M, Pan-Hou H
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Chemosphere. 1997 Feb;34(2):317-24. doi: 10.1016/s0045-6535(96)00379-7.
To investigate the biochemical mechanism responsible for NO-induced neurotoxicity, the effect of sodium nitroprusside(SNP), a NO-generating agent, on PC12 cells was studied. The cell density was dose-dependently inhibited by SNP. Neuronally differentiated PC12 cells showed a higher resistance to SNP than the undifferentiated cells. The inhibitory effect was enhanced by 8-Br-cGMP, and reduced by methylene blue. However, 8-Br-cGMP alone had no significant cytotoxicity. SNP also inhibited [3H]-thymidine incorporation into the cells in a dose-dependent manner. The dose response curves for reducing cell density and for inhibiting thymidine incorporation, were found to be virtually superimposable. These results suggested that cytotoxicity elicited by NO seemed to be due to inhibition of DNA synthesis in PC12 cells.
为了研究一氧化氮(NO)诱导神经毒性的生化机制,我们研究了一种NO生成剂硝普钠(SNP)对PC12细胞的影响。SNP对细胞密度具有剂量依赖性抑制作用。神经元分化的PC12细胞比未分化的细胞对SNP具有更高的抗性。8-溴环鸟苷酸(8-Br-cGMP)增强了这种抑制作用,而亚甲蓝则降低了这种作用。然而,单独的8-Br-cGMP没有明显的细胞毒性。SNP还以剂量依赖性方式抑制[3H] - 胸腺嘧啶核苷掺入细胞。发现降低细胞密度和抑制胸腺嘧啶核苷掺入的剂量反应曲线实际上是重叠的。这些结果表明,NO引起的细胞毒性似乎是由于抑制了PC12细胞中的DNA合成。