Accumulation of alphaB-crystallin in glioma cells and the relation to oncogene expression.
Accumulation of alphaB-crystallin in glioma cells and the relation to oncogene expression.
批准号:
04670213
负责人:
IWAKI Toru
金额:
$1.41万
依托单位:
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
项目状态:
已结题
起止时间:
1992 至 1993
中文摘要
我们已经确定罗森塔尔纤维的一个主要成分是α-晶体蛋白,这是一种主要的晶状体蛋白。正常情况下,α-晶体蛋白在大脑中的数量很少,但在各种病理条件下,它在反应性和肿瘤性胶质细胞以及一些神经元中积聚。因此,α-晶状体蛋白的积累似乎是反应过程的一部分,是形成罗森塔尔纤维所必需的。为了解α-晶状体蛋白在星形胶质细胞Rosenthal纤维中积聚的意义,我们观察了在高温和氧化应激条件下,α-晶状体蛋白在胶质瘤细胞系中的表达和代谢。在两次胁迫后,α-晶状体蛋白的mRNA都增加了,并且α-晶状体蛋白从洗涤剂可溶的形式转变为洗涤剂不能溶解的形式。接下来,我们研究了通过基因操作选择性地改变培养的神经胶质细胞中α-晶体蛋白水平的表型效应。以大鼠C6神经胶质瘤细胞和人U-373 MG神经胶质瘤细胞为研究对象,分别导入大鼠α-晶体蛋白正义和反义基因,改变细胞内α-晶体蛋白的表达水平。Western印迹和免疫细胞化学分析显示,反义策略导致α-晶体蛋白水平下降。α-晶状体蛋白表达的降低伴随着细胞表型的改变:(1)细胞尺寸缩小和/或细胞形态细长;(2)微丝网络紊乱;(3)细胞粘附性降低。像HSP27一样,额外的α-晶体蛋白的存在使稳定的转化子具有耐热表型。因此,胶质瘤细胞中的α-晶状体蛋白在其耐热性中起作用,并可能有助于细胞骨架组织的稳定。
英文摘要
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.
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Yokoyama,N.: "Small heat-shock protein is expresseds in menigiomas and in granulofilamentous inclusion bodies." Acta Neuropathol.85. 248-255 (1993)
Yokoyama,N.:“小热休克蛋白在脑膜瘤和颗粒丝状包涵体中表达。”
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Iwaki,T.: "αB-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers." Am.J.Pathol.143. 487-495 (1993)
Iwaki, T.:“αB-晶状体蛋白和 27-kd 热休克蛋白受中枢神经系统应激条件的调节,并在 Rosenthal 纤维中积累。”143 (1993)。
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Yokoyama,N.: "Small heat-shock protein is expressed in meningiomas and in granulo-filamentous inclusion bodies." Acta Neuropathol.
Yokoyama,N.:“小热休克蛋白在脑膜瘤和颗粒丝状包涵体中表达。”
DOI:
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发表时间:
期刊:
影响因子:
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作者:
[]
通讯作者:
Yokoyama,N.: "Small heat-shock protein is expressed in menigiomas and in granulofilamentous inclusion bodies." Acta Neuropathol.85. 248-255 (1993)
Yokoyama,N.:“小热休克蛋白在脑膜瘤和颗粒丝状包涵体中表达。”
DOI:
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通讯作者:
T.Iwaki, A.Iwaki, J.Tateishi, Y.Sakaki, J.E.Goldman: "alphaB-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers." Am.J.Pathol.143(2). 487-495 (1993)
T.Iwaki、A.Iwaki、J.Tateishi、Y.Sakaki、J.E.Goldman:“αB-晶状体蛋白和 27-kd 热休克蛋白受中枢神经系统应激条件的调节,并在 Rosenthal 纤维中积累。”
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