The effect of age on the activity and molecular properties of human brain monoamine oxidase

Fowler, Christopher J.; Wiberg, A; Oreland, Lars; Marcusson, Jan; Winblad, Bengt

doi:10.1007/bf01249185

Cited by 320 publications

(120 citation statements)

References 30 publications

(21 reference statements)

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“…MAOB activity progressively increases with age and peaks in late adulthood. 58 The MAOA/MAOB activity ratio is higher in fetal (2.43) and neonatal brain (2.39) and decreases in adulthood (0.61). 59 Therefore, MAOA might be more important than MAOB in moderating the effect of traumatic events that occurs during the developmental period.…”

Section: Discussionmentioning

confidence: 99%

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P = 0.005), particularly antisocial alcoholism (P = 0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P = 0.008) and antisocial alcoholics (P = 0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P = 0.006), and to a lesser extent with antisocial alcoholism (P = 0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.

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Section: Discussionmentioning

confidence: 99%

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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“…MAO A are found in catecholaminergic neurons, whereas MAO B are in serotonergic neurons and astrocytes (9, 10). Furthermore, MAO B, but not MAO A, activity increases progressively in the brain throughout adult life (11,12). Aberrant increase of MAO B activity in the elderly has been implicated in neurodegenerative diseases such as Parkinson's disease (13), Alzheimer's disease (14), and Huntington's disease (15).…”

Section: Monoamine Oxidase (Mao)mentioning

confidence: 99%

Activation of Human Monoamine Oxidase B Gene Expression by a Protein Kinase C MAPK Signal Transduction Pathway Involves c-Jun and Egr-1

Wong¹,

Ou²,

Chen³

et al. 2002

Journal of Biological Chemistry

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Monoamine oxidases (MAO)A Monoamine oxidase (MAO)1 plays an important role in the metabolism of biogenic and dietary amines including the neurotransmitters serotonin, norepinephrine and dopamine, and tyramine and benzylamine. The degradation of monoamines by MAO yields hydrogen peroxide (H 2 O 2 ). Located in the outer mitochondrial membrane, the MAO exists in two isoforms (MAO A and MAO B) that exhibit distinct substrate and inhibitor specificity (for a review, see Ref. 1). MAO A deficiency was associated with a syndrome of impulsive aggressive behavior and mild mental retardation in affected males of a Dutch family (2). On the other hand, low platelet MAO B activity was implicated in bipolar disorders, suicidal behavior, alcoholism (3), sensation seeking (4), and poor impulse control (5).Although both MAO A and MAO B are widely distributed in the central nervous system and in the periphery, they differ in cell-and tissue-specific and developmental expressions. For instance, fibroblasts and placenta express predominantly MAO A (6, 7), whereas platelets and lymphocytes express predominantly MAO B (8). MAO A are found in catecholaminergic neurons, whereas MAO B are in serotonergic neurons and astrocytes (9, 10). Furthermore, MAO B, but not MAO A, activity increases progressively in the brain throughout adult life (11,12). Aberrant increase of MAO B activity in the elderly has been implicated in neurodegenerative diseases such as Parkinson's disease (13), Alzheimer's disease (14), and Huntington's disease (15).The human MAO A and MAO B are encoded by two different genes located on the X chromosome (Xp11.2-11.4) (16). The two genes consist of 15 exons with identical exon-intron organization (17) and share 70% sequence similarity in amino acid sequence (18). The 5Ј-flanking sequences of MAO A and MAO B genes have been sequenced and characterized. The maximal promoter activities for MAO A and MAO B genes were found to be in the Ϫ206/Ϫ60 and Ϫ246/Ϫ99 regions, respectively. Although both of these promoter regions are GC-rich and share ϳ60% sequence identity, they contain a distinct organization of cis-acting elements, which may explain differential expression of the MAO A and MAO B genes (19). In this study, we report the role of phorbol 12-myristate 13-acetate (PMA) in the regulation of MAO A and B genes. We showed that MAO B, but not MAO A, gene expression was rapidly induced following PMA treatment. The region between nucleotides Ϫ246 and Ϫ225 of MAO B promoter was essential for PMA-induced expression. The PMA-responsive region was further refined to a single Sp1/Egr-1/Sp1 overlapping binding site located between nucleotides Ϫ239 and Ϫ227. Our results also show that MAO B promoter activity is regulated via a mitogen activated protein kinase (MAPK) pathway that includes protein kinase C (PKC), Ras, MEK1, MEK3, MEK7, ERK2, JNK1, and p38/RK. EXPERIMENTAL PROCEDURESMaterials-The HepG2 (human hepatocytoma) cell line was purchased from the American Type Culture Collection and grown in Dulbecco's modified Eagle's medium su...

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“…Previous enzymatic assays performed on postmortem human brain tissue suggest that MAO-B levels increase with age (1)(2)(3)(4)(5)(6) and in neurodegenerative disease (7) although there are a few reported exceptions (8 -10). The observed 2-3-fold age-related increase in brain MAO-B levels results in increased oxidative stress that may act as a predisposing factor in the vulnerability of the brain to age-related neurodegenerative diseases such as Parkinson's disease (PD) (11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

“…Oxidative deamination of biogenic amines including dopamine and ␤-phenylethylamine (PEA) 1 by monoamine oxidase B (MAO-B) produces hydrogen peroxide (H 2 O 2 ) as a by-product. Previous enzymatic assays performed on postmortem human brain tissue suggest that MAO-B levels increase with age (1)(2)(3)(4)(5)(6) and in neurodegenerative disease (7) although there are a few reported exceptions (8 -10).…”

mentioning

confidence: 99%

Oxidative α-Ketoglutarate Dehydrogenase Inhibition via Subtle Elevations in Monoamine Oxidase B Levels Results in Loss of Spare Respiratory Capacity

Kumar

Nicholls

Andersen

2003

Journal of Biological Chemistry

114

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Age-related increases in brain monoamine oxidase B (MAO-B) and its ability to produce reactive oxygen species as a by-product of catalysis could contribute to neurodegeneration associated with Parkinson's disease. This may be via increased oxidative stress and/or mitochondrial dysfunction either on its own or through its interaction with endogenous or exogenous neurotoxic species. We have created genetically engineered dopaminergic PC12 cell lines with subtly increased levels of MAO-B mimicking those observed during normal aging. In our cells, increased MAO-B activity was found to result in increased H 2 O 2 production. This was found to correlate with a decrease in mitochondrial complex I activity which may involve both direct oxidative damage to the complex itself as well as oxidative effects on the tricarboxylic acid cycle enzyme ␣-ketoglutarate dehydrogenase (KGDH) which provides substrate for the complex. Both complex I and KGDH activities have been reported to be decreased in the Parkinsonian brain. These in vitro events are reversible by catalase addition. Importantly, MAO-B elevation was found to abolish the spare KGDH threshold capacity, which can normally be significantly inhibited before it affects maximal mitochondrial oxygen consumption rates. Our data suggest that H 2 O 2 production via subtle elevations in MAO-B levels can result in oxidative effects on KGDH that can compromise the ability of dopaminergic neurons to cope with increased energetic stress.

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The effect of age on the activity and molecular properties of human brain monoamine oxidase

Cited by 320 publications

References 30 publications

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Activation of Human Monoamine Oxidase B Gene Expression by a Protein Kinase C MAPK Signal Transduction Pathway Involves c-Jun and Egr-1

Oxidative α-Ketoglutarate Dehydrogenase Inhibition via Subtle Elevations in Monoamine Oxidase B Levels Results in Loss of Spare Respiratory Capacity

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