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通过细胞器特异性抗体揭示的肌萎缩侧索硬化症运动神经元高尔基体碎片化

Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis revealed by organelle-specific antibodies.

作者信息

Mourelatos Z, Adler H, Hirano A, Donnenfeld H, Gonatas J O, Gonatas N K

机构信息

University of Pennsylvania School of Medicine, Philadelphia 19104.

出版信息

Proc Natl Acad Sci U S A. 1990 Jun;87(11):4393-5. doi: 10.1073/pnas.87.11.4393.

DOI:10.1073/pnas.87.11.4393
PMID:2349244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC54116/
Abstract

Many studies have established the central involvement of the Golgi apparatus in the transport and processing of plasma membrane, lysosomal, and secreted proteins. The Golgi apparatus of neurons is also involved in the axoplasmic flow of fast-moving macromolecules and in the orthograde, retrograde, and transsynaptic transport of exogenous ligands. Markers of the Golgi apparatus, based on traditional methods of enzyme cytochemistry, are not applicable to human tissues obtained at autopsy. For that reason, the Golgi apparatus of brain cells has not been examined adequately in diseases of the human nervous system. Here we report that an antiserum raised against MG-160, a 160-kDa sialoglycoprotein of medial cisternae of the Golgi apparatus of several rat cells, is a specific and easily reproducible immunocytochemical marker of the Golgi apparatus of human neurons and other cells obtained at autopsy. Application of this probe in amyotrophic lateral sclerosis has shown a fragmentation of the Golgi apparatus in motor neurons similar to that induced by depolymerization of microtubules. We suggest that the fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis has functional implications because significant reductions of secretion of insulin and immunoglobulins have been observed in islet cells and plasma cells, respectively, treated with microtubule-disrupting agents.

摘要

许多研究已证实高尔基体在质膜、溶酶体及分泌蛋白的运输和加工过程中起核心作用。神经元的高尔基体还参与快速移动大分子的轴浆运输以及外源性配体的顺行、逆行和跨突触运输。基于传统酶细胞化学方法的高尔基体标志物并不适用于尸检获取的人体组织。因此,在人类神经系统疾病中,脑细胞的高尔基体尚未得到充分研究。在此我们报告,一种针对MG - 160(几种大鼠细胞高尔基体中间潴泡的一种160 kDa唾液酸糖蛋白)产生的抗血清,是一种特异性且易于重现的免疫细胞化学标志物,可用于标记尸检获取的人类神经元及其他细胞的高尔基体。将该探针应用于肌萎缩侧索硬化症研究发现,运动神经元中的高尔基体出现碎片化,类似于微管解聚所诱导的情况。我们认为,肌萎缩侧索硬化症中运动神经元高尔基体的碎片化具有功能意义,因为在用微管破坏剂处理的胰岛细胞和浆细胞中,分别观察到胰岛素和免疫球蛋白的分泌显著减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/203ed6c77071/pnas01036-0380-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/db8f4561fd31/pnas01036-0379-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/a169c591ba48/pnas01036-0380-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/203ed6c77071/pnas01036-0380-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/db8f4561fd31/pnas01036-0379-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/a169c591ba48/pnas01036-0380-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bb/54116/203ed6c77071/pnas01036-0380-b.jpg

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