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
MAO B 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 (RARalpha) and
retinoid X receptor alpha (RXRalpha). 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 RARalpha 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. RARalpha physically interacts with Sp1 via zinc finger domains in Sp1 as determined by co-immunoprecipitation assay. Further, RARalpha 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.