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Accumulation of alphaB-crystallin in glioma cells and the relation to oncogene expression.

胶质瘤细胞中αB-晶状体蛋白的积累及其与癌基因表达的关系。

基本信息

批准号：
04670213
负责人：
IWAKI Toru
金额：
$ 1.41万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670213/
关键词：
alphaB-ctystallin heat shock protein brain tumor glioma regulation of expression oncogene alphaB-クリスタリン

项目摘要

We have identified a major component of Rosenthal fibers as alphaB-crystallin, a major lens protein. The amount of alphaB-crystallin normally present in the brain is small, but it accumulates in reactive and neoplastic glial cells and in some neurons in a variety of pathologic conditions. Thus, the accumulation of alphaB-crystallin appears to be a part of a reactive process and is required for the formation of Rosenthal fibers. To understand the significance of the accumulation of alphaB-crystallin in Rosenthal fibers within astrocytes, the expression and metabolism of alphaB-crystallin in glioma cell lines were examined under the condition of heat and oxidative stress. alphaB-crystallin mRNA was increased after both stresses and alphaB-crystallin protein moved from a detergent-soluble to a detergent-insoluble form. Next we investigated the phenotypic effects of selectively altering the levels of alphaB-crystallin in cultured glial cells by genetic manipulation. Rat C6 glioma cells and human U-373MG glioma cells were transfected with a rat alphaB-crystallin sense cDNA or an antisense cDNA to alter cellular levels of alphaB-crystallin. The anti-sense strategy resulted in decreased alphaB-crystallin levels, as revealed by Western blot and immunocytochemical analyzes. The reduced alphaB-crystallin expression was accompanied by alterations in cellular phenotype : (1)a reduction of cell size and/or a slender cell morphology ; (2)a disorganized microfilament network ; and (3)a reduction of cell adhensiveness. Like HSP27, the presence of additional alphaB-crystallin protein confers a thermoresistant phenotype to stable tranfectants. Thus, alphaB-crystallin in glioma cells plays a role in their thermal resistance and may contribute to the stability of cytoskeletal organization.

我们已经鉴定出 Rosenthal 纤维的主要成分是 αB-晶状体蛋白，这是一种主要的晶状体蛋白。大脑中正常存在的 αB-晶状体蛋白的量很少，但它会在反应性和肿瘤性神经胶质细胞以及各种病理条件下的一些神经元中积累。因此，αB-晶状体蛋白的积累似乎是反应过程的一部分，并且是罗森塔尔纤维形成所必需的。为了了解星形胶质细胞内罗森塔尔纤维中αB-晶状体蛋白积累的意义，在热和氧化应激条件下检测了神经胶质瘤细胞系中αB-晶状体蛋白的表达和代谢。两种应激后，αB-晶状体蛋白 mRNA 均增加，并且 αB-晶状体蛋白从洗涤剂可溶形式转变为洗涤剂不溶形式。接下来，我们研究了通过基因操作选择性改变培养的神经胶质细胞中 αB-晶状体蛋白水平的表型效应。用大鼠αB-晶状体蛋白有义cDNA或反义cDNA转染大鼠C6神经胶质瘤细胞和人U-373MG神经胶质瘤细胞，以改变αB-晶状体蛋白的细胞水平。蛋白质印迹和免疫细胞化学分析表明，反义策略导致 αB-晶状体蛋白水平降低。 αB-晶状体蛋白表达的减少伴随着细胞表型的改变：(1)细胞尺寸减小和/或细长的细胞形态； (2)无组织的微丝网络； (3)细胞粘附性降低。与 HSP27 一样，额外的 αB-晶状体蛋白的存在赋予稳定转染子耐热表型。因此，神经胶质瘤细胞中的αB-晶状体蛋白在其耐热性中发挥作用，并可能有助于细胞骨架组织的稳定性。