Nguyen Steve M, Alexejun Christa N, Levin Leonard A
Antioxid Redox Signal. 2003 Oct;5(5):629-34. doi: 10.1089/152308603770310293.
Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. Elucidation of the sequence of intracellular events proximal to caspase activation may allow development of effective neuroprotective strategies. In this study, we explored the role that reactive oxygen species may have in signaling RGC apoptosis after axonal injury. Using the fluorescent probe dihydroethidium, we were able to measure intracellular superoxide anion production. We found that axotomized RGCs exposed to oxidative stress exhibited a secondary superoxide burst. The broad-spectrum caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethyl ketone did not block the burst, suggesting it is proximal to caspase activation, but it was inhibited by cycloheximide, consistent with a requirement for protein synthesis. These results are consistent with RGC axotomy inducing synthesis of one or more proteins that mediate oxidative amplification. This could be an early event in signaling of RGC apoptosis after axonal injury.
视网膜神经节细胞（RGCs）在轴突损伤后会发生凋亡。阐明半胱天冬酶激活近端的细胞内事件序列可能有助于开发有效的神经保护策略。在本研究中，我们探讨了活性氧在轴突损伤后RGC凋亡信号传导中可能发挥的作用。使用荧光探针二氢乙锭，我们能够测量细胞内超氧阴离子的产生。我们发现，暴露于氧化应激的轴突切断的RGCs表现出继发性超氧爆发。广谱半胱天冬酶抑制剂Z-缬氨酸-丙氨酸-DL-天冬氨酸-氟甲基酮不能阻断这种爆发，表明它在半胱天冬酶激活近端，但它被环己酰亚胺抑制，这与蛋白质合成的需求一致。这些结果与RGC轴突切断诱导一种或多种介导氧化放大的蛋白质的合成一致。这可能是轴突损伤后RGC凋亡信号传导的早期事件。
