Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: Gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes
Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: Gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes
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DOI：
10.1093/jnen/61.1.12
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发表时间：
2002-01-01
影响因子：
3.2
通讯作者：
Lassmann, H
中科院分区：
文献类型：
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作者：
Bauer, J;Bradl, M;Lassmann, H
关于蛋白质从少突胶质细胞体（它）髓鞘转运的研究揭示了不同转运途径的存在。蛋白脂质蛋白（PLP）在粗面内质网（ER）合成，然后通过高尔基体加工并转运到髓鞘膜，而髓鞘碱性蛋白（MBP）在细胞突起的末端局部合成，其信使RNA被翻译到无油核糖体。PLP从细胞体转运到突起的损伤会干扰其他膜蛋白如髓磷脂相关糖蛋白（MAG）和髓磷脂少突胶质细胞糖蛋白（MOG）的转运，但不会干扰外周翻译的MBP。此外，它还阻碍非髓鞘蛋白的转运，例如淀粉样前体蛋白（APP）。在超微结构水平上，这些代谢紊乱的少突胶质细胞的ER显示脑池极度肿胀，免疫组化显示ER伴侣分子BiP/GRP 78和ER折叠酶蛋白二硫键异构酶（PDI）的强烈表达。这些特征表明，这些少突胶质细胞，这是发现专门在灰质地区的脊髓，开始在未折叠的蛋白质反应，而遭受内质网应激。这些被干扰的少突胶质细胞中的一些被认为是经历程序性细胞死亡。这些结果表明，灰质少突胶质细胞与白色少突胶质细胞的不同之处在于它们通过未折叠蛋白质反应来稳定代谢紊乱的能力。
Studies dealing with transport of proteins from the oligodendrocyte cell body it) the myelin sheath reveal the presence of different transport pathways. Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes, Myelin basic protein (MBP) on the other hand is synthesized locally at the ends of cell processes where its messenger RNA is translated Oil free ribosomes, Here we show that in rats that overexpress PLP. impairment of PLP transport front the cell body to the processes interferes with the translocation of other membrane proteins such as myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG), but not with peripherally translated MBP. In addition, it also impedes the transport of non-myelin proteins, for example the amyloid precursor protein (APP). At the ultrastructural level, the ER of these metabolically disturbed oligodendrocytes revealed extreme swelling of the cisternae, and immunohistochemistry revealed intense expression of the ER chaperone molecule BiP/GRP78 and ER folding enzyme protein disulfide isomerase (PDI). These features Suggest that these oligodendrocytes, which were found exclusively in gray matter areas of the spinal cord, started in unfolded protein response while suffering from ER stress. Some of these disturbed oligodendrocytes were seen to undergo programmed cell death. These results indicate that gray matter oligodendrocyte differ from white matter Oligodendrocytes in their capacity to stabilize metabolic disturbances by an unfolded protein response.