ETHANOL AND NERVOUS SYSTEM DEGENERATION

乙醇与神经系统退化

• 批准号: 3821273
• 负责人: H C PANT
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821273
• 关键词: Wernicke Korsakoff syndrome; alcoholism /alcohol abuse; axon; brain metabolism; calcium metabolism; cytoskeleton; enzyme substrate; ethanol; ganglions; histopathology; ions; neural degeneration; neurochemistry; neurofilament; neurotoxins; peptidases; proteolysis; saltwater environment; toxin metabolism

Brain damage occurs in over 60% of chronic alcoholics. The causes an pathophysiology of this damage, however, are poorly understood. The general goal of our research has been to evaluate the factors that lead to alcohol-induced degeneration of the nervous system in experimental animals. Ethanol has been shown to release calcium from intracellular storage sites (U. Pande and H.C. Pant, Neuroscience 9: 1235, 1983; J.B. Hoek and E. Rubin 13th International Congress of Biochem. 28, 1985). The increase in cytosolic calcium activates proteases cause proteolysis of cytoskeletal proteins. The possibility exist that some of the effects of alcohol-induced degeneration may be to the activation of these proteases. In order to investigate the role of intracellular calcium during neuronal degeneration we have used the squid giant axon as a model system. The advantages of using this preparation are that the enzyme and substrates can be extruded in high yield from the giant axon, thus avoiding contamination of the preparation with nonaxonal enzymes, which may become nonspecifically attached during the homogenization of whole tissue. Second, enzyme activities and substrates present in axoplasm and axoplasmic preparations can e compared with the activities and substrates present in the region of the stellite ganglion, which contains the cell bodies of the giant axon. In the squid axon and cell body we have identified a number of immunoreactive degradation products after calcium-activated proteolysis. The results suggest that an elevation of cytosolic ionized calcium may result in a breakdown of proteins.

超过60%的慢性酗酒者会出现脑损伤。 的 导致这种损伤的病理生理学，然而， 明白 我们研究的总体目标是评估 导致酒精诱导的退化的因素 实验动物的神经系统。 乙醇已经被证明 从细胞内储存位点释放钙（U. pande和 H.C. Pant，Neuroscience 9：1235，1983; J.B. Hoek和E.鲁宾 第13届国际生物化学大会，28，1985）。 增加 在胞质中，钙激活蛋白酶， 细胞骨架蛋白 有可能是一些 酒精诱导的变性可能是激活 这些蛋白酶。 为了研究 在神经元变性过程中的细胞内钙， 乌贼巨大的轴突作为模型系统。 的优越性 这种制备是酶和底物可以 从巨大的轴突中挤出，从而避免 制剂被非轴突酶污染， 在均质化过程中可能变得非特异性附着 整个组织。 第二，酶活性和底物存在 在轴浆和轴浆制备物中， 活动和底物存在于该地区的星状 神经节，其中包含巨大轴突的细胞体。 在 鱿鱼轴突和细胞体，我们已经确定了一些 钙激活后的免疫反应性降解产物 蛋白水解 结果表明，细胞质的升高， 离子化的钙可导致蛋白质的分解。