文章基本信息

标题：Cloning of monkey RALDH1 and characterization of retinoid metabolism in monkey kidney proximal tubule cells
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作者：Helene Brodeur ; Isabelle Gagnon ; Sylvie Mader 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2003
卷号：44
期号：2
页码：303-313
DOI：10.1194/jlr.M200359-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：All- trans and 9- cis retinoic acids function as ligands for retinoic acid receptors (RARs and RXRs), which are ligand-dependent transcription factors and play important roles in development and cellular differentiation. Several retinal dehydrogenases are likely to contribute to the production of all- trans and 9- cis RAs in vivo, but their respective roles in different tissues are still poorly characterized. We have previously characterized and cloned from kidney tissues the rat retinal dehydrogenase type 1 (RALDH1), which oxidizes all- trans and 9- cis retinal with high efficiency but is inactive with 13- cis retinal. Here we have characterized the retinal-oxidizing activity in monkey JTC12 cells, which are derived from kidney proximal tubules. In vitro assay of cell lysates revealed the presence of a NAD⁺-dependent dehydrogenase that catalyzed the oxidation of all- trans , 9- cis, and 13- cis retinal. Northern blot analysis of JTC12 RNAs and cloning by reverse transcription-polymerase chain reaction demonstrated expression of a monkey homolog of RALDH1. Bacterially expressed JTC12 RALDH1 catalyzed conversion of all three retinal isomers, with a higher catalytic efficiency for 9- cis retinal than for all- trans and 13- cis retinal. Accordingly, live JTC12 produced 9- cis retinoic acid more efficiently than all- trans retinoic acid from their respective retinal precursors. Only metabolites corresponding to the same steric conformation were formed from 9- cis or all- trans retinal, indicating a lack of detectable isomerizing activity in JTC12 cells.