Retinoic Acid Activates Monoamine Oxidase B Promoter in Human Neuronal Cells

Monoamine oxidase (MAO) B deaminates a number of biogenic and dietary amines and plays an important role in many biological processes. Among hormonal regulations of MAO B, we have recently found that retinoic acid (RA) significantly activates both MAOB promoter activity and mRNA expression in a human neuroblastoma BE(2) C cell line. RA activates MAO B promoter in both concentration- and time-dependent manners, which is mediated through retinoic acid receptor alpha (RAR alpha) and retinoid X receptor alpha (RXR alpha). There are four retinoic acid response elements (RAREs) as identified in the MAO B 2-kb promoter, and mutation of the third RARE reduced RA-induced MAO B promoter activation by 50%, suggesting this element is important. Electrophoretic mobility shift analysis and chromatin immunoprecipitation assay demonstrated that RAR alpha specifically binds to the third RARE both in vitro and in vivo. Moreover, transient transfection and luciferase assays revealed that Sp1 enhances but not essentially required for the RA activation of MAO B through two clusters of Sp1-binding sites in the MAO B promoter. RAR alpha physically interacts with Sp1 via zinc finger domains in Sp1 as determined by co-immunoprecipitation assay. Further, RAR alpha was shown to be recruited by Sp1 and to form a transcriptional regulation complex with Sp1 in the Sp1-binding sites of natural MAO B promoter. Taken together, this study provides evidence for the first time showing the stimulating effect of RA on MAO B and new insight into the molecular mechanisms of MAO B regulation by hormones.