Uto A, Dux E, Kusumoto M, Hossmann K A
Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Cologne, Germany.
J Neurochem. 1995 May;64(5):2185-92. doi: 10.1046/j.1471-4159.1995.64052185.x.
The effect of three metabolic inhibitors--iodoacetate, potassium cyanide, and potassium arsenate--on neuronal viability was studied in primary rat cortical and hippocampal CA1 neuronal cultures. Iodoacetate (0.1 mM) applied for 5 min to 8-day-old cultures resulted in delayed neuronal death within 3-24 h in cortical and hippocampal CA1 neurons. Neuronal degeneration was preceded by transient inhibition of energy metabolism to approximately 40% and a permanent inhibition of protein synthesis to approximately 50%. The inhibition of protein synthesis and the neuronal death were prevented by the free radical scavenger vitamin E but not by the glutamate antagonist MK-801. Removal of calcium during iodoacetate exposure could not protect against toxicity, and there was no increase of intracellular calcium concentration during and shortly after iodoacetate treatment. Cyanide and arsenate produced only partial neuronal degeneration, even at a dose of 10 mM. These observations demonstrate that brief exposure of neurons to low concentrations of iodoacetate produces a delayed type of neuronal death that is not mediated by either calcium or glutamate. The therapeutic effect of vitamin E points to a free-radical mediated injury and suggests that this type of pathology may also be involved in delayed neuronal death after transient energy depletion in vivo.
在原代大鼠皮质和海马CA1神经元培养物中，研究了三种代谢抑制剂——碘乙酸盐、氰化钾和砷酸钾——对神经元活力的影响。将碘乙酸盐（0.1 mM）应用于8日龄培养物5分钟，导致皮质和海马CA1神经元在3 - 24小时内出现延迟性神经元死亡。在神经元变性之前，能量代谢短暂抑制至约40%，蛋白质合成永久抑制至约50%。自由基清除剂维生素E可防止蛋白质合成抑制和神经元死亡，而谷氨酸拮抗剂MK - 801则不能。在碘乙酸盐暴露期间去除钙不能防止毒性，并且在碘乙酸盐处理期间及处理后不久细胞内钙浓度没有增加。即使在10 mM的剂量下，氰化物和砷酸盐也仅产生部分神经元变性。这些观察结果表明，神经元短暂暴露于低浓度碘乙酸盐会产生一种延迟性神经元死亡类型，其不是由钙或谷氨酸介导的。维生素E的治疗作用表明存在自由基介导的损伤，并提示这种病理类型也可能参与体内短暂能量消耗后的延迟性神经元死亡。
