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PubMed1979

Monoamine oxidase in platelets and brains of non-psychiatric and non-neurological geriatric patients.

Monoamine oxidase (MAO) activity has previously been found to be high both in brain and in platelets in patients with Alzheimer's disease and low in patients with cycloid psychosis and suicidal behaviour and/or ethanol abuse. To establish if there is a correlation between brain and platelet MAO activities in patients without psychic disease, blood samples from patients in a geriatric ward were collected before death and from 4 different parts of the brain at autopsy. The MAO activities in platelets and brain were then estimated with different substrates. No correlation between the MAO activities in the two tissues was, however, found, regardless of the substrate used.

Age Factors↗

PubMed1980

A sensitive and rapid fluorimetric assay for monoamine oxidase utilizing high pressure liquid chromatography.

A rapid and sensitive assay for the measurement of monoamine oxidase (MAO) activity was developed. This method utilizes high pressure liquid chromatography with fluorescence excitation at 280 nm and detection of 330 nm at pH 5.0 of indoleacetic acid and 5-hydroxyindoleacetic acid, the deaminated products of two substrates for MAO, tryptamine, and serotonin, respectively. The assay allows for the complete separation of metabolites from either of the two substrates. The method has been used to determine MAO activity in the frontal cortex and caudate nucleus of rat brain using tryptamine and serotonin as substrates. The ease and rapidity of this assay make it sutable for use where routine enzyme determinations are required.

Animals↗

PubMed1982

Effects of monoamine oxidase inhibitors on performance during differential reinforcement of low response rate.

The effects of three monoamine oxidase inhibitors (MAOI) on performance under a differential-reinforcement-of-low-rate 72-s schedule (DRL 72-s) for water reinforcement were determined. All three drugs (isocarboxazid, iproniazid, phenelzine) reduced response rate and increased reinforcement rate in rats performing under the DRL schedule. Drugs from other classes (alcohol, chlordiazepoxide, morphine, pentobarbital) did not produce similar effects. The ability of MAOI to increase reinforcement rate under a DRL 72-s schedule is similar to that recently reported for tricyclic antidepressants and the two atypical antidepressants mianserin and iprindole. These findings support the contention that the DRL schedule may be useful as a test for identifying new antidepressants and for elucidating the neurochemical effects of antidepressants that are responsible for their therapeutic actions.

Animals↗

PubMed1992

An enzyme immunoassay for the measurement of human monoamine oxidase B protein.

A heterologous, competitive, solid phase ELISA has been developed which can measure monoamine oxidase (MAO) B concentration (both inactive and active) in human platelets and other tissue extracts. The assay is based on competition between a soluble form of MAO and MAO bound to a solid phase for binding to a limiting amount of a MAO B-specific monoclonal antibody, 3F12/G10. It utilises a crude and easily prepared sample of human liver mitochondrial membranes as the source of solid phase MAO. Optimal assay conditions allow detection of MAO B down to at least 0.5 ng (4.18 fmol; 6.25 ng/ml) of protein. As the assay is sensitive and simple to operate, it will allow a systematic assessment of the role of platelet MAO concentrations in the aetiology of psychiatric and neurologic conditions.

Adult↗

PubMed1988

Alteration of platelet serotonergic mechanisms and monoamine oxidase activity in premenstrual syndrome.

Platelet uptake and content of 5-hydroxytryptamine (5-HT), platelet monoamine oxidase (MAO) activity, and plasma free and total tryptophan levels were determined in patients diagnosed with premenstrual syndrome (PMS) and in control subjects. The Vmax of 5-HT uptake and 5-HT content in platelets of PMS patients were significantly decreased during the premenstrual phase (cycle days -9 to -1) compared to control subjects. Platelet MAO activity was significantly lower postmenstrually (cycle days 5-9) in PMS patients compared to the premenstrual phase. There were no differences in plasma free and total tryptophan levels between PMS patients and control subjects during either interval. As platelets are believed to be a peripheral model for central serotonergic neurons, the results suggest that PMS symptomatology may be related to alterations in serotonergic neuronal mechanisms.

Adult↗

PubMed1976

The reaction of sulfhydryl reagents with bovine hepatic monoamine oxidase. Evidence for the presence of two cysteine residues essential for activity.

The bovine liver monoamine oxidase (EC 1.4.3.4) was found to be inactivated by various well-known sulfhydryl reagents like p-mercuribenzoate, methylmercuric iodide and 5,5'-dithiobis-(2-nitro benzoic acid). The present investigation shows that the inactivation of the enzyme results from reactions of these reagents with 2 out of 8 titratable sulfhydryl groups per 10(5) g of the enzyme. The substrate, benzylamine, and competitive inhibitors like benzaldehyde, p-nitrobenzaldehyde, benzyl alcohol protected the enzyme from inactivation by the mercurials or the Ellman reagent. The inactivation experiments with these sulfhydryl reagents, the protection experiments, and the kinetics as well as physicochemical observations suggest that there are only two cysteine residues that are required for activity of the enzyme. It is possible that these two residues may be active-center residues.

Animals↗

PubMed2003

Effects of zinc ion on type A monoamine oxidase in monkey brain mitochondria.

The effects of ZnSO(4) on types A and B monoamine oxidase (MAO) isozymes in monkey brain mitochondria were investigated, in vitro. Type A MAO activity in monkey brain decreased to about 50% with 1 microM ZnSO(4) using serotonin as a substrate, and this inhibition was proportional to the concentration of ZnSO(4). ZnSO(4) had no effect, however, on type B MAO activity in monkey brain using beta-phenylethylamine as a substrate. The inhibition by ZnSO(4) of type A MAO activity was competitive and reversible. ZnSO(4) did not inhibit either type A or type B MAO activity in rat brain mitochondria. Almost similar results were also obtained when ZnCl(2) was used, in vitro. These results indicate that the inhibiting action of zinc ion differs depending on animal species and organ. Type A MAO in monkey brain mitochondria was highly sensitive to zinc ion, while type B activity was less sensitive.

Analysis of Variance↗

PubMed1994

Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1.

The core promoter region of human monoamine oxidase (MAO) A has been identified in the two 90 bp repeat sequences, which can be further divided into four imperfect tandem repeats, each containing an Sp 1 binding site in the reversed orientation. Gel retardation and DNase 1 footprinting assays identified Sp 1 to be the major transcription factor binding to MAO A core promoter. In addition, positive association has been observed between cellular Sp1 concentration and MAO A promoter or catalytic activity, indicating that Sp1 is a controlling factor for human MAO A expression. DNA fragments from MAO A core promoter exhibit promoter activity in both orientations in a transient transfection assay, using human growth hormone as the reporter gene. A DNA probe isolated from upstream of the core promoter detected positive signals in a Northern analysis, suggesting that the reverse promoter activity may endogenously transcribe a new gene located upstream of MAO A.

Base Sequence↗

PubMed1977

Effects of the eye enucleation on the activity of monoamine oxidase and acetylcholinesterase in the superior colliculus of the rat.

Changes in the activity of monoamine oxidase (MAO) and acetylcholinesterase (AChE) following unilateral eye enucleation were measured for the superior colliculus (SC), lateral geniculate body (LGB), and nucleus suprachiasmaticus (NSC) in the rat by means of microspectrophotometry. The most conspicuous change of high significance was the decrease of MAO activity in the superficial strata of the SC contralateral to the enucleated eye. The other layers of SC, such as the stratum opticum, the intermediate strata, the deep strata and the central gray did not show significant postoperative changes in MAO acitivity. MAO activity of the LGB and the NSC was also not affected to a significant degree. The site of decrease of MAO activity in the superficial strata of the SC sould be degenerating optic nerve terminals. The strong AChE activity in the superficial strata may be derived from the horizontal cells. AChE activity in the SC showed only slight postoperative changes. The possible roles of the monoaminergic and cholinergic systems in the process of visual information are discussed.

Acetylcholinesterase↗

PubMed1983

In vivo, noradrenaline is a substrate for rat brain monoamine oxidase A and B.

In vivo clorgyline (5 mg/kg) and (-)-deprenyl (5 mg/kg) selectively inhibit monoamine oxidase (MAO) type A and B activities in rat brain hypothalamus and caudate nucleus using 5-hydroxytryptamine (5-HT), noradrenaline (NA), and beta-phenylethylamine (PEA) as substrates. Clorgyline induces a significant increase in NA concentrations of hypothalamus and caudate nucleus; however (-)-deprenyl is without effect. The combination of clorgyline and (-)-deprenyl at the above doses completely inhibits both forms of MAO, resulting in an even greater increase in NA levels in both brain areas than observed with clorgyline. The non-selective inhibitor tranylcypromine (5 mg/kg) produced a similar effect. Rats pretreated with the selective or the non-selective inhibitors but given L-DOPA (50 mg/kg) have a similar pattern of brain NA, but its concentrations are higher in both brain regions. The results indicate that although in vitro NA may be an exclusive substrate for MAO type A, in vivo, when this enzyme form is selectively inhibited, NA at high concentrations can be a substrate for MAO type B.

Animals↗

PubMed1997

A one-step fluorometric method for the continuous measurement of monoamine oxidase activity.

We have developed a one-step fluorometric method for the measurement of monoamine oxidase (MAO) activity in 96-well microplates with sensitivity 10-fold higher than the conventional spectrophotometric assay method. This assay is based on the detection of H2O2 in a horseradish peroxidase-coupled reaction using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and stable probe for H2O2. With a single sampling, this assay is useful for performing both end-point and continuous measurements of MAO activity. Using a commercially available enzyme, our assay allows the detection of MAO B activity as low as 1.2 x 10(-5) U/ml. When applied to crude tissue homogenates, we have been able to selectively detect both MAO A and MAO B from cow brain tissue with protein content as low as 200 microgram per sample. The potential applications of this assay include the measurement of MAO activity in normal and diseased tissues, blood samples, and other biological fluids and the screening of drugs for the treatment of MAO-mediated diseases.

Animals↗

PubMed1984

Platelet monoamine oxidase activity in schizophrenia: relationship to family history of the illness and neuroleptic treatment.

Platelet monoamine oxidase (MAO) activity was determined in a large population of drug-free and haloperidol-treated schizophrenic patients and healthy controls and, in a second study, in a sample of schizophrenics after a wash-out period and at different times during treatment with haloperidol. Enzyme activity was significantly decreased in both acute and chronic haloperidol-treated schizophrenics, but not in drug-free schizophrenics, compared with normal controls. No significant difference was observed between drug-free schizophrenics with a family history of the illness and those without such history, and between healthy relatives of schizophrenic patients and normal controls without a family history of schizophrenia. MAO activity was significantly reduced after 14 and 21 days of haloperidol treatment, and such reduction did not correlate with response to treatment. These data strongly support the idea that neuroleptic intake may, at least in part, explain low MAO values repeatedly reported in schizophrenics.

Adolescent↗

PubMed2000

Monoamine oxidase B induces ERK-dependent cell mitogenesis by hydrogen peroxide generation.

The mitochondrial enzyme monoamine oxidase (MAO) A and B catalyze the oxidative deamination of various endogenous and exogenous biogenic amines. In the present study, we used human embryonic kidney 293 (HEK 293) cells stably transfected with human MAO-B cDNA to investigate the potential role of hydrogen peroxide (H(2)O(2)) produced by MAO-B isoform as an intracellular messenger involved in regulation of cell signaling and function. The MAO substrate tyramine induced tyrosine phosphorylation of Shc, ERK activation, and an increase in DNA synthesis in HEK 293 expressing MAO-B, but not in wild type HEK 293 cells, which do not express MAO. Tyramine effects were fully prevented by cell pretreatment with the MAO inhibitor pargyline or the antioxidant N-acetylcysteine. These results show that MAO-B induces MAPK/ERK activation and cell mitogenesis through H(2)O(2) production.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Low platelet monoamine oxidase activity in Swedish imprisoned criminal offenders.

Numerous studies report a connection between low platelet monoamine oxidase activity (trbc MAO) and personality traits such as impulsiveness and sensation seeking. Generally, criminal offenders constitute a group of individuals that are high in such temperamental characteristics. In this study, we investigated trbc MAO activity in imprisoned criminal offenders and in controls where the confounding factor of smoking was under control. Radiometric MAO assays were performed in 99 male criminal offenders and in 60 non-criminal volunteers. Offenders had significantly lower trbc MAO activity than controls, i.e., 8.8 +/- 3.0 nmol/10(10) platelets/mm and 11.3 +/- 5.1, respectively (p<0.0001). When only smoking individuals were included in the analysis, the difference in trbc MAO was still statistically significant (p<0.05). Based on these data, we suggest that trbc MAO is related to mechanisms predisposing for development of specific personality characteristics that in turn increase vulnerability for criminal behaviour. The results also suggest that low trbc MAO activity in criminal offenders is not an artefact of cigarette smoking.

Adult↗

PubMed1999

Association of monoamine oxidase B alleles with age at onset in amyotrophic lateral sclerosis.

An active role of monoamine oxidase B (MAO-B) in the pathogenesis of neurodegenerative disorders such as Parkinson's disease has been proposed as the enzyme is known to be a generator of free radicals which seem to be responsible for neuron oxidative damage. We evaluated the influence of MAO-B in the pathogenesis of the sporadic forms of Amyotrophic lateral sclerosis (ALS) by studying the MAO-B allele distribution in 51 patients and 71 healthy controls. MAO-B did not directly result in a risk factor for ALS but seemed to strongly influence age at onset. The mean ALS onset age was significantly higher in individuals carrying allele 5 compared to individuals without this allele (60.4 +/- 8.1 vs. 52.1 +/- 10.3 years; P = 0.004). These results, in agreement with findings in the literature, suggest an increased MAO-B expression in ALS and support the hypothesis that neuronal cell death in neurodegenerative diseases is triggered by astroglial reaction.

Adult↗

PubMed1988

Stereoisomers of allenic amines as inactivators of monoamine oxidase type B. Stereochemical probes of the active site.

The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary alpha-allenic amines have been investigated in detail. The chirality of the allene group in N-methyl-N-aralkylpenta-2,3-dienamines was found to have a profound effect on the inactivation rate, with the (R)-allenes being up to 200-fold more potent than their (S)-allenic counterparts. The ability of (S)-allenes to inactivate MAO was severely compromised by the presence of N-phenethyl or N-alpha-substituted-aralkyl substituents. The opposing chiralities in both the allene and aralkyl groups of (R,R)- and (S,S)-N-methyl-N-(1,2,3,4-tetrahydro-1-naphthyl)-penta-2,3-dienamine+ ++ resulted in a difference of more than 3 orders of magnitude in inactivation rates. The stereoselectivity of MAO-B was examined further with a series of reversible aralkylamine inhibitors; thus (R)-1,2,3,4-tetrahydro-1-naphthylamine was determined to be 150-fold more potent than its enantiomer.

Alkenes↗

PubMed1982

Monoamine oxidase (MAO) activity as a determinant in human neurophysiology.

Several lines of evidence indicate that monoamine oxidase (MAO) activity can regulate levels of biogenic amines and neuronal activity in the nervous system. The two types of MAO activity, A and B, appear to have different domains of activity in the body. Brain tissue has both types of activity, although adrenergic neurons are thought to contain exclusively MAO-A. MAO activity can also be measured in peripheral tissues: MAO-A in cultured skin fibroblasts and placenta, and MAO-B in platelets and lymphocytes. These two types of activity are mediated by different enzyme molecules and are regulated independently by endogenous and exogenous factors including genetic determinants, hormones, and aging. In humans, inhibition of MAO-A activity leads to mood elevation in depressed patients; in contrast, low MAO-B activity in platelets has been associated with an increased susceptibility to psychopathology. In order to assess further the role of MAO activity in human mood and behavior, it will be important to measure both forms of the enzyme independently and to establish correlations between levels of activity and discrete phenotypic traits.

Adrenergic Fibers↗

PubMed1976

Histochemical studies of monoamine oxidase in experimental myocardial infarctions.

Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas.

Animals↗