ROLE OF CALCIUM IN ACRYLAMIDE NEUROTOXICITY

长期接触丙烯酰胺会导致骨骼肌无力 患有远端轴索病症。造成这种情况的生化损伤 神经元损伤尚未确定。最近的研究表明， 多种损伤引起的神经细胞内钙离子浓度升高 过程(例如，化学、疾病)是导致 神经元损伤和/或死亡。因此，丙烯酰胺可能会通过以下方式产生伤害 使细胞膜变得“漏水”，从而允许 胞外钙离子和其他离子。由此导致的增加 胞浆钙通过抑制神经细胞损伤而致神经细胞损伤 线粒体呼吸，通过破坏细胞骨架结构或通过 直接抑制轴突运输。拟议的调查将 确定钙浓度的渐进性增加是否 暂时与丙烯酰胺中毒有关。这些研究将涉及 丙烯酰胺处理大鼠神经组织和神经细胞的应用 暴露在这种神经毒素下的培养系统。具体地说，初步研究 将使用原子吸收分光光度法来测量 丙烯酰胺引起的总钙浓度的变化。中的更改 钙水平将在时间上与糖尿病的发展相关。 丙烯酰胺引起的神经元损伤。将使用放射自显影(45Ca) 鉴定丙烯酰胺处理的大鼠脑内的核或区域 表现出钙摄取和/或滞留的变化。这些区域(例如 小脑)可能代表选择性损伤的结构 丙烯酰胺，因此重要地参与了表现 神经毒性。钙离子和钙离子亚细胞分布的改变 丙烯酰胺产生的其他离子将使用x射线进行测定。 微量分析。用这种技术可以测量离子。 在线粒体和其他亚细胞细胞器中的浓度。丙烯酰胺 神经毒性可能是通过钙离子的抑制作用来实现的。 线粒体呼吸作用。因此，氧摄取量将使用以下方法测量 神经组织和神经细胞培养中的克拉克氧电极 暴露在丙烯酰胺中。这项研究的长期目标是确定 钙在丙烯酰胺诱导的远端轴索病变中的作用 其他神经毒素。这项研究的结果可能涉及一种 钙与人类疾病状态(例如婴儿神经轴突)的关系 营养不良)，与类似于 由丙烯酰胺诱导。

Chronic exposure to acrylamide causes skeletal muscle weakness associated with a distal axonopathy. The biochemical lesion responsible for this neuronal damage has not been identified. Recent research indicates that an increase in intraneuronal calcium induced by a variety of injurious processes (e.g. chemical, disease) is responsible for the resulting neuronal damage and/or death. Thus, acrylamide might produce injury by causing cellular membranes to become "leaky" thereby allowing an influx of extracellular calcium and other ions. The resulting increase in cytoplasmic calcium could cause nerve cell injury by inhibiting mitochondrial respiration, by disrupting cytoskeletal structure or by a direct inhibition of axonal transport. The proposed investigation will determine whether a progressive increase in the concentration of calcium is temporally related to acrylamide intoxication. These studies will involve the use of nervous tissues from acrylamide-treated rats and nerve cell culture systems exposed to this neurotoxin. Specifically, initial studies will employ atomic absorption spectrophotometry to measure acrylamide-induced changes in total calcium concentrations. Changes in calcium levels will be correlated temporally with the development of neuronal damage caused by acrylamide. Autoradiography (45Ca) will be used to identify nuclei or regions in brains from acrylamide-treated rats which exhibit changes in calcium uptake and/or retention. Such areas (e.g. cerebellum) might represent structures which are selectively damaged by acrylamide and therefore are importantly involved in the manifestation of neurotoxicity. Alterations in the subcellular distribution of calcium and other ions produced by acrylamide will be determined using x-ray microanalysis. With this technique it is possible to measure ion concentrations in mitochondria and other subcellular organelle. Acrylamide neurotoxicity might be mediated by the inhibitory effect of calcium on mitochondrial respiration. Therefore, oxygen uptake will be measured using a Clark's oxygen electrode in nervous tissues and in nerve cell cultures exposed to acrylamide. The long range goal of this research is to identify the role of calcium in the distal axonpathy produced by acrylamide and other neurotoxins. Results from this research might implicate an involvement of calcium in human disease states (e.g. infantile neuroaxonal dystrophy) which are associated with neuropathic changes similar to those induced by acrylamide.