A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes
A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes
复制标题
DOI：
10.1074/jbc.272.32.20185
复制
发表时间：
1997-08-08
影响因子：
4.8
通讯作者：
David, S
中科院分区：
文献类型：
--
作者：
Patel, BN;David, S
铜蓝蛋白是一种铜结合蛋白，是肝源性血浆中主要的铁氧化酶。我们现在提供的证据表明，在哺乳动物中枢神经系统的星形胶质细胞表达的一种新的膜结合形式的铜蓝蛋白。使用单克隆抗体（1A1），我们表明该抗体识别的细胞表面抗原是血浆铜蓝蛋白，并且它通过糖基磷脂酰肌醇（GPI）锚直接锚定到细胞表面。我们的肽图谱和其他免疫化学研究表明，除了GPI锚，膜结合和分泌的血浆形式是相似的，我们还表明，铜蓝蛋白的膜结合形式具有氧化酶活性。因此，这些研究表明，GPI锚定形式的铜蓝蛋白可能在氧化亚铁中发挥与分泌形式类似的作用。星形胶质细胞表达的GPI锚定形式的铜蓝蛋白可能是中枢神经系统中该分子的主要形式，因为血清铜蓝蛋白不穿过血脑屏障，中枢神经系统中缺乏这种形式的铜蓝蛋白可能导致产生高毒性的自由基，其可引起神经元变性，如在血浆堆蛋白血症和其它神经变性疾病如帕金森氏病和阿尔茨海默氏病中所见。
Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in plasma of hepatic origin, We now provide evidence for a novel membrane-bound form of ceruloplasmin expressed by astrocytes in the mammalian central nervous system. Using a monoclonal antibody (1A1), we show that the cell surface antigen recognized by this antibody is ceruloplasmin and that it is directly anchored to the cell surface via a glycosylphosphatidylinositol (GPI) anchor, Our peptide mapping and other immunochemical studies indicate that, except for the GPI anchor, the membrane-bound and secreted plasma forms are similar, We also show that the membrane-bound form of ceruloplasmin has oxidase activity. These studies therefore suggest that the GPI-anchored form of ceruloplasmin may play a role similar to the secreted form in oxidizing ferrous iron, The GPI-anchored form of ceruloplasmin expressed by astrocytes is likely to be the major form of this molecule in the central nervous system because serum ceruloplasmin does not cross the blood-brain barrier, Lack of this form of ceruloplasmin in the central nervous system could lead to the generation of highly toxic free radicals, which can cause neuronal degeneration as seen in aceruloplasminemia and other neurodegenerative diseases such as Parkinson's and Alzheimer's disease.