CELLULAR AND MOLECULAR APPROACHES TO NEUROTOXICOLOGY

神经毒理学的细胞和分子方法

• 批准号: 3968974
• 负责人: S J MORRIS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 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/3968974
• 关键词: adenosinetriphosphatase; adrenal medulla; calcium channel blockers; catecholamines; chromaffin cells; electron microscopy; exocytosis; experimental allergic encephalomyelitis; fluorescence; fluorescent dye /probe; freeze etching; heavy metals; membrane activity; membrane fusion; membrane lipids; membrane model; membrane structure; metal poisoning; myelin; neurochemistry; neurotoxins; neurotransmitter metabolism; photochemistry; pinocytosis; sarcoplasmic reticulum; tissue /cell culture; toxicant screening

Neurotoxins are known to disrupt the structure of myelin. The membranes of this ubiquitous material of the nervous system contain three major proteins. Myelin basic protein, which accounts for 30 percent of CNS myelin proteins, has no known physiological function, although injection of purified MBP will cause Experimental Allergic Encephalomyelitis, considered by some as a model for Multiple Sclerosis. A molecular model for the structure of MBP generates a series of testable predictions. We have been examining the structural properties of MBP using fluorescence and optical spectroscopy. Contrary to many reports, we find evidence for extensive long range structural specificity of MBP in agreement with the model. We find that a subfraction of isolated MBP molecules bind heme and other porphyrins with affinities on the order of 10-8 M. These molecules also bind ANS derivatives with affinities on the order of 10-7 M. Heme rapidly displaces bound bis-ANS. These studies may lead to a rapid, more precise functional assay for MBP than the induction of EAE.

众所周知，神经毒素可以破坏髓鞘的结构。的膜 这种无处不在的神经系统物质包含三个主要成分 蛋白质。髓鞘碱性蛋白，占中枢神经系统的30% 髓鞘蛋白，没有已知的生理功能，尽管注射 纯化的MBP将导致实验性变态反应性脑脊髓炎 被一些人视为多发性硬化症的模型。一种新的分子模型 MBP的结构产生了一系列可测试的预测。我们一直在 用荧光和光学方法研究MBP的结构性质 光谱学。与许多报道相反，我们发现了广泛的证据 MBP的长程结构特异性与模型一致。我们 发现分离的MBP分子的一小部分与血红素和其他 具有10-8M量级亲和力的卟啉。这些分子还 快速结合亲和力为10-7M的ANS衍生物 置换绑定的BIS-ANS。 这些研究可能导致一种快速、更准确的MBP功能测定方法 比EAE的诱导作用更强。