cDNA cloning of a novel secreted isoform of the human receptor for advanced glycation end products and characterization of cells co-expressing cell-surface scavenger receptors and Swedish mutant amylo

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• 作者：Malherbe ; Pari ; Richards ; J. Grayson ; Gaillard ; Hé ; lè ; ne ; Thompson ; Annick ; Diener ; Catherine ; et. al.
• 关键词：Receptor for advanced glycation end products ; Secreted isoform ; Amyloid-β ; protein ; Alzheimer's disease ; Scavenger receptor ; AD ; Alzheimer's disease ; Aβ ; β ; -amyloid peptide ; β ; APP ; β ; -amyloid precursor protein ; hRAGE ; human receptor f
• 刊名：Molecular Brain Research
• 出版年：1999
• 出版时间：August 25, 1999
• 年：1999
• 卷：71
• 期：2
• 页码：159-170
• 全文大小：2.20 M

文摘

The receptor for advanced glycation end products (RAGE) has been proposed as a cell surface receptor that binds amyloid-β protein (Aβ), thereby triggering its cytotoxic effects [S.D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, T. Slattery, L. Zhao, M. Nagashima, J. Morser, A. Migheli, P. Nawroth, D. Stern, A.M. Schmidt, RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease, Nature 382 (1996) 685–691.]. A cDNA library of human lung was screened for RAGE with an appropriate hybridization probe. In addition to cell surface RAGE, one clone was found which encodes a new version of RAGE, termed hRAGEsec, which lacks the 19 amino acids of the membrane-spanning region and is therefore secreted. Comparison with the genomic sequence revealed that the synthesis of the secreted isoform requires alternative splicing. The deduced protein sequence of the mature hRAGEsec consists of 321 amino acids with a predicted molecular mass of 35.66 kDa. The pattern of expression of hRAGEsec in human brain was analyzed by in situ hybridization histochemistry. The most intense expression of the gene in contrast to cell surface RAGE was detected in hippocampal CA3 pyramidal cells, dentate gyrus granule cells, cortical neurons as well as glial cells in white matter. To investigate the interaction between Aβ and RAGE and another scavenger receptor, SRA, under physiological conditions, they were co-expressed with human βAPP₆₉₅-SFAD in a human cell and the level of Aβ in the condition medium was assessed by immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) analysis. A nearly 100 % reduction of Aβ from the conditioned medium of hRAGE cells and 40 % reduction from the SRA-cells implied that hRAGE could be a prominent cell surface receptor interacting with Aβ.