Nuutinen Tapio, Huuskonen Jari, Suuronen Tiina, Ojala Johanna, Miettinen Riitta, Salminen Antero
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Neurochem Int. 2007 Feb;50(3):540-7. doi: 10.1016/j.neuint.2006.11.002. Epub 2006 Dec 28.
Recent studies indicate that astrocytes may be the primary target of secreted amyloid-beta 1-42 peptides, with the neurotoxicity representing a secondary response to astrocytic stress. Our purpose was to clarify the astrocytic stress response induced by amyloid-beta peptides in human and rat astrocytes. Human amyloid-beta 1-42 peptides and fibrils induced the appearance of cytoplasmic vacuoles in normal human astrocytes (NHA) and CCFsttg1 astrocytoma cells. Vacuoles appeared 9-12h after the amyloid-beta exposure and remained present for several days. Rat primary neonatal astrocytes showed similar but less prominent vacuolar response. Human amyloid-beta peptides 1-16, 1-28, 10-20, 17-21 and 25-35 did not cause vacuole formation. Electron microscopic observations revealed large endocytic vacuoles containing fibrillar amyloid material. Stress marker analysis did not show any increase in protein levels of HSP70, HSP90, GRP78 and GRP94. However, the protein level of clusterin/apoJ, a secreted chaperone, was strongly increased both in NHA and CCFsttg1 astrocytes. Endocytic response associated with the accumulation of clusterin/apoJ protein suggests that clusterin/apoJ has a role in the clearance of amyloid-beta peptides.
最近的研究表明，星形胶质细胞可能是分泌型淀粉样β蛋白1-42肽的主要靶点，其神经毒性是对星形胶质细胞应激的次级反应。我们的目的是阐明淀粉样β肽在人源和大鼠星形胶质细胞中诱导的星形胶质细胞应激反应。人淀粉样β蛋白1-42肽和纤维在正常人星形胶质细胞（NHA）和CCFsttg1星形细胞瘤细胞中诱导出现细胞质空泡。淀粉样β蛋白暴露后9-12小时出现空泡，并持续数天。大鼠原代新生星形胶质细胞表现出相似但不太明显的空泡反应。人淀粉样β肽1-16、1-28、10-20、17-21和25-35不会导致空泡形成。电子显微镜观察显示，有大量含有纤维状淀粉样物质的内吞空泡。应激标志物分析未显示HSP70、HSP90、GRP78和GRP94的蛋白水平有任何升高。然而，分泌型伴侣蛋白clusterin/apoJ的蛋白水平在NHA和CCFsttg1星形胶质细胞中均显著升高。与clusterin/apoJ蛋白积累相关的内吞反应表明，clusterin/apoJ在淀粉样β肽的清除中起作用。
