Gander Roland, Eller Philipp, Kaser Susanne, Theurl Igor, Walter Doris, Sauper Teresa, Ritsch Andreas, Patsch Josef R, Föger Bernhard
Department of Medicine, University of Innsbruck, Austria.
J Lipid Res. 2002 Apr;43(4):636-45.
Phospholipid transfer protein (PLTP) plays an important role in plasma lipoprotein metabolism. However, PLTP is expressed in a wide range of tissues suggesting additional local functions. To analyze the tissue distribution of PLTP in an animal with high-level expression of the structurally and functionally related CETP, we have cloned the full-length cDNA of rabbit PLTP (1,796 bp). Rabbit PLTP cDNA shows high homology to human, murine, and porcine PLTP cDNA, averaging 86.1%, 80.4%, and 86.1%, respectively. Interestingly, the C-terminus contains a unique seven amino acid insertion not found in previously characterized mammalian PLTPs. In clear contradistinction to human PLTP, rabbit PLTP mRNA was prominent in brain. In situ hybridization studies revealed specific, high-level synthesis of PLTP mRNA in choroid plexus and ependyma, the organs responsible for production of cerebrospinal fluid. Consistent with these findings, PLTP activity in cerebrospinal fluid amounted to 23% +/- 3% of that in rabbit plasma. In contrast, neither CETP mRNA nor CETP activity were detectable in rabbit brain.A role of PLTP in the central nervous system could involve some of its actions previously established in vitro, like proteolysis of apolipoproteins, and be physiologically relevant for neurodegenerative disorders such as Alzheimer's disease.
磷脂转运蛋白（PLTP）在血浆脂蛋白代谢中起重要作用。然而，PLTP在多种组织中表达，提示其具有其他局部功能。为分析PLTP在结构和功能相关的胆固醇酯转运蛋白（CETP）高表达动物中的组织分布，我们克隆了兔PLTP的全长cDNA（1796 bp）。兔PLTP cDNA与人、小鼠和猪的PLTP cDNA具有高度同源性，平均分别为86.1%、80.4%和86.1%。有趣的是，其C末端含有一个独特的七氨基酸插入序列，这在先前已鉴定的哺乳动物PLTP中未发现。与人类PLTP明显不同的是，兔PLTP mRNA在脑中含量丰富。原位杂交研究显示，脉络丛和室管膜（负责产生脑脊液的器官）中PLTP mRNA有特异性的高水平合成。与这些发现一致，脑脊液中的PLTP活性相当于兔血浆中PLTP活性的23%±3%。相反，在兔脑中未检测到CETP mRNA和CETP活性。PLTP在中枢神经系统中的作用可能涉及其先前在体外确定的一些作用，如载脂蛋白的蛋白水解作用，并且在诸如阿尔茨海默病等神经退行性疾病中具有生理相关性。
