Journal article
Retinoic acid activates monoamine oxidase B promoter in human neuronal cells
The Journal of biological chemistry, Vol.284(25), pp.16723-16735
06/19/2009
PMCID: PMC2719307
PMID: 19401466
Abstract
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.
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Details
- Title
- Retinoic acid activates monoamine oxidase B promoter in human neuronal cells
- Creators
- Jason B Wu - Washington State University, Pharmaceutical Sciences, Department ofKevin Chen - University of Southern CaliforniaXiao-Ming Ou - University of Mississippi Medical CenterJean C Shih - University of Southern California
- Publication Details
- The Journal of biological chemistry, Vol.284(25), pp.16723-16735
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Grant note
- R01 MH39085 / NIMH NIH HHS R0 1MH67968 / NIMH NIH HHS
- Identifiers
- 99900620488701842
- Language
- English
- Resource Type
- Journal article