LENS PROTEIN ALPHA-CRYSTALLIN B CHAIN

脊椎动物晶状体的主要元素α-B-晶状体蛋白也是 在豆状核外组织中表达。最近的发现表明，阿尔法- B-晶状体蛋白应该被认为是一种“热休克”或“应激”蛋白质。 首先，α-晶体蛋白与α-晶体蛋白家族有相同的序列 低分子量热休克蛋白(HSPs)。第二，尽管α-B-晶状体蛋白是 在一些组织中结构性表达，可以上调 戏剧性地被各种经典的“压力剂”，包括热 休克、氧化应激和过渡金属。一个奇特的例子 α-B-晶状体蛋白在儿童脑白质营养不良中表达， 亚历山大病，星形胶质细胞积聚大量蛋白质 被称为罗森塔尔纤维的包裹体。这些产品的主要组成部分 包裹体为α-B晶相和与之相关的小分子热震 蛋白质，热休克蛋白27。在这笔赠款的头两年里，我们发现 a)。α-B-晶体蛋白和热休克蛋白27的mRNA和蛋白水平为 亚历山大病中枢神经系统显著升高(B)。星形胶质细胞上调 这两个基因既协调又独立地响应一种 各种“应激剂”，以及c)。α-B-晶体蛋白对星形胶质细胞的保护作用 细胞免受盐浓度升高的胁迫。我们建议 继续我们对亚历山大病的研究并将重点放在调控上 小分子热休克蛋白在中枢神经系统中的表达 遵循以下几条路线：I.其他热休克蛋白是否在 亚历山大病，如果是这样，它们是否参与了RP的形成？二、有没有 应激诱导星形胶质细胞α-B-晶状体蛋白和热休克蛋白27的表达 发生在转录水平上吗？III.我们能否确定起作用的蛋白质 作为α-B-晶体蛋白和Hsp27的转录调控因子？做这些事吧 蛋白质在应激反应中起作用？这些蛋白质是在 亚历山大病及其在压力累积中的作用 亚历山大中枢神经系统中的蛋白质？IV.α-B-晶状体蛋白对细胞有保护作用吗 从特定的“压力”，或具有一般的保护属性 顶住了许多“压力”？

Alpha-B-crystallin, a major element of the vertebrate lens, is also expressed in extralenticular tissues. Recent findings indicate that alpha- B-crystallin should be considered a "heat shock" or "stress" protein. First, the alpha-crystallins share homologous sequences with the family of low MW heat shock proteins (hsps). Second, although alpha-B-crystallin is constitutively expressed in some tissues, it can be upregulated dramatically by a variety of classical "stress agents, including heat shock, oxidative stress, and transitional metals. A singular example of alpha-B-crystallin expression occurs in the childhood leukodystrophy, Alexander disease, in which astrocytes accumulate large, proteinaceous inclusions known as Rosenthal fibers. The major components of these inclusions are alpha-B-crystallin and the related small MW heat shock protein, hsp27. Over the first two years of this grant we have found that a). levels of mRNA and protein for alpha-B-crystallin and hsp 27 are markedly elevated in Alexander disease CNS, b). astrocytes upregulate these two genes both coordinately and independently in response to a variety of "stress" agents, and c). alpha-B-crystallin protects astroglial cells from the stress of increased salt concentration. We propose to continue our studies on Alexander disease and to focus on the regulation of small MW heat shock proteins in the central nervous system and shall follow several lines of inquiry: I. Are other hsps overexpressed In Alexander disease and if so, are they involved in RP formation? II. Does the stress-induced increase in alpha-B-crystallin and hsp27 in astrocytes occur at a transcriptional level? III. Can we identify proteins that act as transcriptional regulators for alpha-B-crystallin and hsp27? Do these proteins function in stress responses? Are these proteins expressed in Alexander disease and might they play a role in the accumulation of stress proteins in the Alexander CNS? IV. Does alpha-B-crystallin protect cells from specific "stresses" or does it have general protective properties against many "stresses"?