Identification of human monoamine oxidase (MAO) A and B gene promoters

Shih, Jean C.; Qs, Zhu; Grimsby, Joseph; Chen, K.

doi:10.1007/978-3-7091-9324-2_3

Cited by 6 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both isoforms are nonselective for dopamine, tyramine, and tryptamine (37). The gene encoding MAO-A is localized on the X chromosome and has a distinct pattern of cis-regulatory elements in its promoter region when compared with the MAO-B gene (39,40). Its basic promoter contains four stimulating protein 1 binding sites and reporter gene assays indicated that three of them are functional (40).…”

Section: Discussionmentioning

confidence: 99%

Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A

Chaitidis

Billett

O'Donnell

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Monocyte/macrophage function is critically regulated by specific cytokines and growth factors that they are exposed to at inflammatory sites. IL-4 and IL-13 are multifunctional cytokines generated mainly by Th2 lymphocytes that have important biological activities in allergy and inflammation. The Th2 response of human peripheral monocytes is characterized by complex alterations in the gene expression pattern, which involves dominant expression of CD23 cell surface Ag and lipid-peroxidizing 15-lipoxygenase-1 (15-LOX1). In this study, we report that the classical Th2 cytokines IL-4 and IL-13 strongly up-regulate expression of monoamine oxidase A (MAO-A) with no induction of the closely related isozyme, MAO-B. Real-time PCR indicated a >2000-fold up-regulation of the MAO-A transcripts, and immunohistochemistry revealed coexpression of the enzyme with 15-LOX1 in a major subpopulation of monocytes. MAO-A was also induced in lung carcinoma A549 cells by IL-4 in parallel with 15-LOX1. In promyelomonocytic U937 cells, which neither express 15-LOX1 nor MAO-A in response to IL-4 stimulation, expression of MAO-A was up-regulated following transfection with 15-LOX1. This is the first report indicating expression of MAO-A in human monocytes. Its isoform-specific up-regulation in response to Th2 cytokines suggests involvement of the enzyme in modulation of innate and/or acquired immune system.

show abstract

Section: Discussionmentioning

confidence: 99%

Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A

Chaitidis

Billett

O'Donnell

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The published sequence of the MAOA gene contains four exact repeats of a 30-bp sequence located at positions -1142 to -1262 relative to the ATG translation initiation codon, or approximately 1-1.2 kb upstream of the mapped transcription initiation sites (Zhu et al 1992(Zhu et al , 1994Denney et al 1994;Shih et al 1993Shih et al , 1994Shih et al , 1995. This sequence is internally repetitive in that it consists of 5 repetitions of the core sequence ACC(A/G/C)G(C/T).…”

Section: A Vntr Upstream Of Maoamentioning

confidence: 99%

A functional polymorphism in the monoamine oxidase A gene promoter

Sabol¹,

Hu²,

Hamer³

1998

Hum Genet

989

1,011

View full text Add to dashboard Cite

We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2-10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA.

show abstract

“…Such a transcriptional program might function by altering the synthesis of four groups of proteins: (1) proteins that serve to control gene transcription; similarly to the decrease in c-JUN that we have found, other transcriptional inducers (see Dragunow and Preston136 for a review of transcriptional inducing protein in apoptosis) linked to neurodegeneration might be modulated by (-)-deprenyl, such as glyceraldehyde 3-phosphate dehydrogenaseZo1 or N F K~~~~~~~~; (2) proteins that modulate apoptosis, such as the interleukin converting enzymes (see above); (3) proteins that influence oxidative radical formation; as well as the SOD family and GPx, recent has shown that (-)-deprenyl increased nitric oxide synthetase in hippocampal cells damaged by DSP-4; and (4) proteins that bind cytosolic Ca++ levels, such as calbindin. Groups 2, 3, and 4 would serve to maintain A?…”

Section: (-)-Deprenyl Alters the Expression Of Genes That Influence Mmentioning

confidence: 99%

“…paminergic neurotransmission by three different mechanisms: (1) inhibition of the oxidative deamination of dopamine t o 3,4-dihydroxyphenylacetic acid (DOPAC), which would increase the available pool of dopamine for reuptake into nerve terminals and subsequent releasel4J5; 2) facilitation of dopaminergic transmission by the trace amine phenylethylaminephenylethylamine is degraded by MAO-B, and this deprenyl-induced MAO-B inhibition could increase phenylethylamine levels, which might potentiate the activation of dopamine receptors by dopamine,lfi and (3) (-1-deprenyl may increase dopaminergic reuptake into synaptic terminals and thereby increase the pool of dopamine available for re1ea~e.l~ These actions on dopaminergic neurotransmission would be symptomatic, that is, they would provide benefits in PD and possibly AD by facilitating dopaminergic transmission but would not alter the neurodegenerative process.…”

mentioning

confidence: 99%

Modulation of gene expression rather than monoamine oxidase inhibition

Tatton¹

1996

Neurology

158

View full text Add to dashboard Cite

(-)-Deprenyl has been used to irreversibly inhibit monoamine oxidase B (MAO-B) in Parkinson's disease (PD) and Alzheimer's disease (AD) as a possible means of improving dopaminergic neurotransmission or of reducing neuronal necrosis caused by oxidative radical damage. Recent research in tissue culture and animal models has shown that (-)-deprenyl can reduce neuronal apoptosis caused by a variety of agents, in a variety of neuronal subtypes through a mechanism(s) that does not require MAO-B inhibition. Studies using general P450 blockers have shown that one of the principal metabolites of (-)-deprenyl, (-)-desmethyldeprenyl, mediates the antiapoptotic action. Other research has shown that (-)-deprenyl can induce altered expression of a number of genes in preapoptotic neurons both in vitro and in vivo, including the genes for superoxide dismutase (SOD) 1 and 2, BCL-2 and BCL-XL, nitric oxide synthase, c-JUN, and nicotinamide adenine dinucleotide dehydrogenase. Antiapoptosis by (-)-deprenyl is associated with a prevention of a progressive reduction of mitochondrial membrane potential in preapoptotic neurons, which has been shown to occur early in apoptosis and is likely an initiating factor. The above changes in gene expression appear to reduce oxidative radical damage to mitochondria and maintain mitochondrial permeability, thereby blocking mitochondrial "signals" that initiate apoptosis. In situ evidence suggests that apoptosis contributes to neuronal death in a number of neurodegenerative diseases. If apoptosis is critical to the progression of one or more human neurodegenerative diseases, then transcriptionally active agents such as (-)-desmethyldeprenyl may be of value in treating the diseases. The kinetics of (-)-deprenyl metabolism, however, and its biodistribution after oral administration, make it unlikely that the antiapoptotic action has played a major role in benefits found for the drug in PD and AD to date.

show abstract

Identification of human monoamine oxidase (MAO) A and B gene promoters

Cited by 6 publications

References 10 publications

Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A

Th2 Response of Human Peripheral Monocytes Involves Isoform-Specific Induction of Monoamine Oxidase-A

A functional polymorphism in the monoamine oxidase A gene promoter

Modulation of gene expression rather than monoamine oxidase inhibition

Contact Info

Product

Resources

About