Differential regulation of monoamine oxidase A and B genes

UnrestrictedThis study has investigated the transcriptional regulation of MAO A and B genes. MAO A and B are a crucial pair of oxidative isoenzymes, which degrade biogenic and dietary amines, including monoamine neurotransmitters, and produce hydrogen peroxide. Abnormal MAO A or B activity has been implicated in numerous neurological and psychiatric disorders. These two isoenzymes have different but overlapping substrate and inhibitor selectivity. There is a 70% amino acid sequences identity and different tissue- and cell-specific expression between the two enzymes. MAO A and B promoters share approximately 60% sequence identity with distinct organization. Both MAO A and B are regulated by Sp-family proteins, such as Sp1 and Sp3. MAO B is uniquely regulated by protein kinase C and mitogen-activated protein kinase signaling pathways, whereas MAO A is involved in the c-Myc-induced proliferative signaling pathway.; This study further demonstrates the similar and unique transcriptional regulation of MAO A and B genes. The results show that the SRY (the sex-determining region Y) gene activates the MAO A but not the MAO B gene; in contrast, the antioxidant t-butylhydroquinone (tBHQ) only represses MAO B activity. The SRY gene, encoding a putative transcription factor responsible for sex determination during embryogenesis, activates MAO A gene expression through a functional SRY-binding site in MAO A promoter, which is synergistically enhanced by Sp1. On the other hand, tBHQ represses MAO B activity through the Akt signaling pathway and cell cycle progression, and the downstream cyclin D1 directly regulates MAO B. Moreover, we demonstrate that RA activates MAO B transcription through both effective retinoic acid response elements and Sp1 sites in the promoter, which involves crosstalk between the retinoic acid receptor alpha and Sp1 in MAO B core promoter region.; In summary, these studies identified novel regulators of the MAO A and B genes and their molecular mechanisms and suggested novel potential role(s) of MAO in certain physiological processes and diseases states. The differential regulation of MAO A and B genes further supports the different physiological functions of these two isoenzymes