Wang W, Post J I, Dow K E, Shin S H, Riopelle R J, Ross G M
Department of Pediatrics, Queen's University, Kingston, Ontario, Canada.
Neurosci Lett. 1999 Jan 8;259(2):115-8. doi: 10.1016/s0304-3940(98)00929-x.
We have previously provided evidence that two transition metal cations, Zn2+ and Cu2+, can alter the conformation of nerve growth factor (NGF), rendering it unable to bind to its receptors or to activate signal transduction pathways. In the present study, we have assessed the influence of Zn2+ and Cu2+ on NGF-mediated protection from an oxidative insult. Exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide resulted in an increase in cell death via apoptosis, which was inhibited by NGF. Zn2+ and Cu2+, when added to cultures at a concentration of 100 microM, prevented NGF-mediated survival-promoting effects. Neither of these ions had an effect on basal cell viability (in the absence of NGF) after an oxidative insult. These results demonstrate that Zn2+ and Cu2+ can selectively inhibit NGF-mediated resistance to an oxidative stress, and have significant implications for neuronal function under both physiological and pathological (e.g. cerebral ischemia) conditions.
我们之前已提供证据表明，两种过渡金属阳离子Zn2+和Cu2+可改变神经生长因子（NGF）的构象，使其无法与其受体结合或激活信号转导途径。在本研究中，我们评估了Zn2+和Cu2+对NGF介导的抗氧化损伤保护作用的影响。将大鼠嗜铬细胞瘤（PC12）细胞暴露于过氧化氢会导致通过凋亡引起的细胞死亡增加，而NGF可抑制这种增加。当以100微摩尔的浓度添加到培养物中时，Zn2+和Cu2+会阻止NGF介导的促生存作用。在氧化损伤后，这两种离子对基础细胞活力（在无NGF的情况下）均无影响。这些结果表明，Zn2+和Cu2+可选择性抑制NGF介导的对氧化应激的抗性，并且对生理和病理（例如脑缺血）条件下的神经元功能具有重要意义。
