A CELLULAR-MODEL OF OXIDANT-MEDIATED NEURONAL INJURY
A CELLULAR-MODEL OF OXIDANT-MEDIATED NEURONAL INJURY
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DOI：
10.1016/0006-8993(93)91110-e
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发表时间：
1993-06-25
期刊：
影响因子：
2.9
通讯作者：
HYSLOP, PA
中科院分区：
文献类型：
--
作者：
HINSHAW, DB;MILLER, MT;HYSLOP, PA
氧的部分还原产生的氧化剂被认为在神经元损伤中起着重要作用。我们利用PC-12大鼠嗜铬细胞瘤细胞系建立了过氧化氢(H_2O_2)介导的神经元损伤的细胞模型。用荧光显微镜观察了经神经生长因子诱导分化的PC12细胞在过氧化氢损伤后轴突内微管和微丝的结构。H_2O_2浓度低至100微米时，微管解聚在3-4小时内形成一个初始的周期模式，然后发展到完全解聚。含有肌动蛋白细丝的神经元微刺相对比微管更能抵抗H_2O_2的损伤。H_2O_2损伤后PC_(12)细胞体和突起也可见气泡，气泡内可见微管。影响神经结构的破坏性改变发生在PC12细胞溶解之前，但不是必需的。细胞暴露于钙离子载体后，离子霉素(25um)也能引起与H_2O_2损伤后相同的微管解聚，提示H_2O_2可能通过升高细胞内Ca~(2+)来介导其对神经突起的破坏作用。
Oxidants derived from the partial reduction of oxygen are thought to play a significant role in neuronal injury. We present here a cellular model of neuronal injury mediated by hydrogen peroxide (H2O2) using the PC 12 rat pheochromocytoma cell line. The organization of microtubules and microfilaments within neurites of PC 12 cells differentiated by exposure to nerve growth factor was examined after H2O2 injury using fluorescence microscopy. Concentrations of H2O2 as low as 100 muM produced an initial periodic pattern of microtubule depolymerization over 3-4 h which later progressed to complete depolymerization. Neuritic microspikes containing actin filaments were relatively more resistant to injury by H2O2 than microtubules. Blebbing of PC 12 cell bodies and neurites also was seen after H2O2 injury and the blebs appeared to contain microtubules. The destructive changes affecting neuritic structure preceded but were not essential for PC 12 cell lysis. Exposure of the cells to the Ca2+ ionophore, ionomycin (25 muM) also produced the same pattern of microtubule depolymerization in PC 12 neurites as was seen after H2O2 injury suggesting that H2O2 may mediate its destructive effect on the neurites via elevation of intracellular Ca2+.