High Monoamine Oxidase Activity Research Articles

Identification of a Lactic Acid Bacteria to Degrade Biogenic Amines in Chinese Rice Wine and Its Enzymatic Mechanism.

A L. plantarum, CAU 3823, which can degrade 40% of biogenic amines (BAs) content in Chinese rice wine (CRW) at the end of post-fermentation, was selected and characterized in this work. It would be an optimal choice to add 106 cfu/mL of selected strain into the fermentation broth to decrease the BAs while keeping the character and quality of CRW. Nine amine oxidases were identified from the strain and separated using Sephadex column followed by LC-MS/MS analysis. The purified amine oxidase mixture showed a high monoamine oxidase activity of 19.8 U/mg, and more than 40% of BAs could be degraded. The biochemical characters of the amine oxidases were also studied. This work seeks to provide a better solution to degrade BAs in CRW prior to keeping the character and quality of CRW and a better understanding of the degradability of the strain to the BAs.

Effects of dissolved oxygen availability and culture biomass at induction upon the intracellular expression of monoamine oxidase by recombinant E. coli in fed batch bioprocesses

The effects of oxygen availability and induction culture biomass upon production of an industrially important monoamine oxidase (MAO) were investigated in fed-batch cultures of a recombinant E. coli. For each induction cell biomass 2 different oxygenation methods were used, aeration and oxygen enriched air. Induction at higher biomass levels increased the culture demand for oxygen, leading to fermentative metabolism and accumulation of high levels of acetate in the aerated cultures. Paradoxically, despite an almost eight fold increase in acetate accumulation to levels widely reported to be highly detrimental to protein production, when induction wet cell weight (WCW) rose from 100% to 137.5%, MAO specific activity in these aerated processes showed a 3 fold increase. By contrast, for oxygenated cultures induced at WCW's 100% and 137.5% specific activity levels were broadly similar, but fell rapidly after the maxima were reached. Induction at high biomass levels (WCW 175%) led to very low levels of specific MAO activity relative to induction at lower WCW's in both aerated and oxygenated cultures. Oxygen enrichment of these cultures was a useful strategy for boosting specific growth rates, but did not have positive effects upon specific enzyme activity. Based upon our findings, consideration of the amino acid composition of MAO and previous studies on related enzymes, we propose that this effect is due to oxidative damage to the MAO enzyme itself during these highly aerobic processes. Thus, the optimal process for MAO production is aerated, not oxygenated, and induced at moderate cell density, and clearly represents a compromise between oxygen supply effects on specific growth rate/induction cell density, acetate accumulation, and high specific MAO activity. This work shows that the negative effects of oxygen previously reported in free enzyme preparations, are not limited to these acellular environments but are also discernible in the sheltered environment of the cytosol of E. coli cells.

Functionally undefined gene, yggE, alleviates oxidative stress generated by monoamine oxidase in recombinant Escherichia coli

Real-time PCR analysis showed that yggE gene was about two and three times up-regulated in Escherichia coli cells exposed to UVA irradiation and thermal elevation, respectively, suggesting that this gene is responsive to physiological stress. The yggE gene was introduced into E. coli BL21 cells, together with a monoamine oxidase (MAO) gene as a model source for oxidative stress generation. The distribution of independently isolated transformants (two dozen isolates) was examined in terms of MAO activity and cell vitality. In the case of control strain expressing MAO alone, the largest number of transformants existed in the low range of MAO activity less than 2 units mg(-1) and the number significantly decreased at increased MAO activity. On the other hand, the distribution of MAO/YggE-coexpressing transformants shifted to higher MAO activity with frequent appearance in the activity range of 4-8 units mg(-1). The yggE gene product therefore has a possible function for alleviating the stress generated in the cells.

Association of 5‐HTT gene polymorphism, platelet MAO activity, and drive for thinness in a population‐based sample of adolescent girls

Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects. The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales--Drive for Thinness and Bulimia--were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR. Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness. The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity.

Both low and high activities of platelet monoamine oxidase increase the probability of becoming a smoker

Platelet monoamine oxidase (MAO) activity is a marker of personality and psychiatric vulnerability, but the direct inhibitory action of tobacco constituents on the enzyme distorts the association. In the present investigation, data from a prospective longitudinal study of smoking behaviour and platelet MAO activity in adolescents at ages 15 and 18 years were sequentially analysed using a second-order multiple logistic regression analysis. The odds of regular smoking at 18 years increased significantly with increasing absolute deviation of platelet MAO activity at 15 years from the mean. That is, both low and high platelet MAO activity at 15 years predicted a higher probability of becoming a smoker. These data suggest that smoking is associated with low platelet MAO activity not only because of the direct inhibitory effect of tobacco constituents on the enzyme, but also because subjects with low platelet MAO activity are more likely to become smokers. Furthermore, the possible association between above-average platelet MAO activity and behavioural phenotypes should be reexamined.

Oxygen dependency of monoamine oxidase activity in the intact lung.

Hydrogen peroxide generated by monoamine oxidase (MAO)-mediated deamination of biogenic amines has been implicated in cell signaling and oxidative injury. Because the pulmonary endothelium is a site of metabolism of monoamines present in the venous return, this brings into question a role for MAO in hyperoxic lung injury. The objective of this study was to evaluate the O(2) dependency of the MAO reaction in the lung. To this end, we measured the pulmonary venous effluent concentrations of the MAO substrate [(14)C]phenylethylamine and its metabolite [(14)C]phenylacetic acid after the bolus injection of either phenylethylamine or phenylacetic acid into the pulmonary artery of perfused rabbit lungs over a range of PO(2) values from 16 to 518 Torr. The apparent Michaelis constant for O(2) was approximately 18 microM, which is more than an order of magnitude less that measured for purified MAO. The results suggest a minimal influence of high O(2) on MAO activity in the normal lung and demonstrate the importance of measuring reaction kinetics in the intact organ.

Submitochondrial Distribution of Three Key Steroidogenic Proteins (Steroidogenic Acute Regulatory Protein and Cytochrome P450scc and 3β-Hydroxysteroid Dehydrogenase Isomerase Enzymes) upon Stimulation by Intracellular Calcium in Adrenal Glomerulosa Cells

In adrenal glomerulosa cells, angiotensin II (Ang II) and potassium stimulate aldosterone synthesis through activation of the calcium messenger system. The rate-limiting step in steroidogenesis is the transfer of cholesterol to the inner mitochondrial membrane. This transfer is believed to depend upon the presence of the steroidogenic acute regulatory (StAR) protein. The aim of this study was 1) to examine the effect of changes in cytosolic free calcium concentration and of Ang II on intramitochondrial cholesterol and 2) to study the distribution of StAR protein in submitochondrial fractions during activation by Ca2+ and Ang II. To this end, freshly prepared bovine zona glomerulosa cells were submitted to a high cytosolic Ca2+ clamp (600 nM) or stimulated with Ang II (10 nM) for 2 h. Mitochondria were isolated and subfractionated into outer membranes, inner membranes (IM), and contact sites (CS). Stimulation of intact cells with Ca2+ or Ang II led to a marked, cycloheximide-sensitive increase in cholesterol in CS (to 143 +/- 3. 2 and 151.1 +/- 18.1% of controls, respectively) and in IM (to 119 +/- 5.1 and 124.5 +/- 6.5% of controls, respectively). Western blot analysis revealed a cycloheximide-sensitive increase in StAR protein in mitochondrial extracts of Ca2+-clamped glomerulosa cells (to 159 +/- 23% of controls). In submitochondrial fractions, there was a selective accumulation of StAR protein in IM following stimulation with Ca2+ (228 +/- 50%). Similarly, Ang II increased StAR protein in IM, and this effect was prevented by cycloheximide. In contrast, neither Ca2+ nor Ang II had any effect on the submitochondrial distribution of cytochrome P450scc and 3beta-hydroxysteroid dehydrogenase isomerase. The intramitochondrial presence of the latter enzyme was further confirmed by immunogold staining in rat adrenal fasciculata cells and by immunoblot analysis in MA-10 mouse testicular Leydig cells. These findings demonstrate that under acute stimulation with Ca2+-mobilizing agents, newly synthesized StAR protein accumulates in IM after transiting through CS. Moreover, our results suggest that the import of StAR protein into IM may be associated with cholesterol transfer, thus promoting precursor supply to the two first enzymes of the steroidogenic cascade within the mitochondria and thereby activating mineralocorticoid synthesis.

Annual Variations in Hypothalamic Serotonin and Monoamine Oxidase in the Catfish Heteropneustes fossilis with a Note on Brain Regional Differences of Day-Night Variations in Gonadal Preparatory Phase

In Heteropneustes fossilis, significant annual variations in serotonin (5-HT) and monoamine oxidase (MAO) were found in the hypothalamus both at 12 and 24 hr with high values of content and turnover index (TI) during gonadal recrudescence, and low values during gonadal quiescence. The 5-HT content reached high levels during April-July (late preparatory, prespawning, and spawning phases). The TI of 5-HT showed two peaks in its midday value: a major peak occurred in March (midpreparatory phase) and a minor one in June (prespawning phase). High MAO activity was seen in June (prespawning phase) and low values during February, March, and April (preparatory phase). Significant day-night variations in 5-HT content and TI, and MAO activity were observed in the hypothalamus and telencephalon in February and March (early and midpreparatory phase), but not at other times of the year. In the whole brain and separate regions such as the thalamus, midbrain, and hindbrain no day-night patterns were seen. A comparison of the data shows that the increase in 5-HT content and TI from February to March was significantly higher in the hypothalamus than in telencephalon and the opposite is true for MAO. The results suggest that the high hypothalamic activities of 5-HT and MAO during recrudescence is related to breeding activity; the day-night variations during the early and midpreparatory phase in these variables may be related to initiation of breeding in this species.

Monoamine oxidases of the brains and livers of macaque and cercopithecus monkeys

We assessed the two forms of monoamine oxidase (MAO), MAO-A and MAO-B, in discrete regions of the brain and in cerebral micro- and macrovessels, choroid plexus, and liver of three species of monkeys: African Green, rhesus, and cynomolgus. MAO was determined by specific [ 3H]pargyline binding which is stoichiometric and irreversible and by measuring the rate of oxidation of several substrates. Cerebral micro- and macrovessels had low MAO content. Regional brain MAO did not vary by more than one-fold in the brains of each of the three species of monkeys and was higher in the basal ganglia than in the cerebral cortex or cerebellum. MAO in the choroid plexus was low, while the liver had higher MAO activity than any of the brain samples. The vast majority of MAO in all the tissues that we examined was of the MAO-B type, and specific [ 3H]pargyline binding correlated well with the oxidation rate of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These results show marked similarities in brain MAO distribution between monkey and man. Of the three monkey species, the African Green monkey had the lowest MAO activity in its cerebral microvessels, which constitute the blood-brain barrier, although the small number of observations in each group did not allow statistical analyses of the differences.

Correlation of MPTP neurotoxicity in vivo with oxidation of MPTP by the brain and blood-brain barrier in vitro in five rat strains

We studied 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in 5 strains of rats by assessing mortality and brain monoamine changes after MPTP injections into the internal carotid artery. We then attempted to correlate the differences among rat strains in their susceptibility to MPTP neurotoxicity in vivo with MPTP oxidation by monoamine oxidase (MAO) of the cerebral cortex, striatum, and brain microvessels in vitro. Despite the fact that the carotid route delivers much higher amounts of MPTP to the ipsilateral cerebrum than can be achieved by systemic injections, no significant dopamine depletion occured in ipsilateral striata of Sprague-Dawley rats (the most resistant strain), but significant reductions of about 40% in striatal dopamine were evident in the more sensitive strains. Decreased striatal dopamine levels in these latter rat strains were associated with increased dopamine turnover. Higher doses of MPTP resulted in acute death. MPTP-induced mortality was not affected, but striatal dopamine depletion was prevented, by MAO inhibition. Differences among rat strains in their susceptibility to MPTP neurotoxicity correlated best with MAO activity in their isolated brain microvessels, but not with MAO activity in their striata or cerebral cortices. These results are consistent with the hypothesis that the rats' resistance to MPTP neurotoxicity is to some extent a property of their unique brain endothelium which has high MAO activity.

Effect of monoamine oxidase inhibition on catecholamine levels: evidence for synthesis but not storage of epinephrine in rat spinal cord

Epinephrine levels in the intermediolateral cell group in the rat spinal cord are very low, although there is a dense projection to this region from cells containing all the enzymes required for epinephrine biosynthesis. One explanation for this finding is that epinephrine in the nerve terminals is degraded as soon as it is synthesized, so that no epinephrine is actually stored in synaptic vesicles. To test this hypothesis, epinephrine levels were measured in spinal cord of rats pretreated with an inhibitor of monoamine oxidase, the major enzyme involved in epinephrine degradation. Selected other tissues (i.e. brainstem, hypothalamus, adrenal gland, superior cervical ganglion) were examined for comparison. Pargyline treatment (75 mg/kg i.p., 4 h prior to sacrifice) increased catecholamine levels in spinal cord, hypothalamus, and brainstem. However, the percent increase in epinephrine in the spinal cord and brainstem was much larger than that for dopamine and norepinephrine in the 3 central nervous system regions studied, as well as larger than that for epinephrine in the hypothalamus. These results suggest that phenylethanolamine N-methyltransferase (PNMT)-containing terminals in the rat spinal cord can synthesize epinephrine, but that little if any epinephrine is stored in synaptic vesicles due to the rapid metabolism of cytoplasmic catecholamines by monoamine oxidase. In contrast, pargyline pretreatment had no effect on catechol levels in the adrenal gland, suggesting that little metabolism of catecholamines takes place in those epinephrine-synthesizing cells. Furthermore, since pargyline pretreatment increased norepinephrine levels but decreased dopamine levels in the superior cervical ganglion, it is suggested that most of the dopamine in that sympathetic ganglion is present as a precursor to norepinephrine in noradrenergic postganglionic sympathetic neurons. Additional studies were performed using neonatal rats, since it has been reported that spinal cord epinephrine levels are much higher in neonates than in adults. Epinephrine levels were found to be higher in the spinal cords of neonates compared to adults, but were increased to a lesser extent by monoamine oxidase inhibition. These results suggest that the interaction of monoamine oxidase with epinephrine synthesis is such that high monoamine oxidase activity can prevent the storage of epinephrine in certain nerve terminals containing the enzymes required to synthesize epinephrine. This raises the possibility that PNMT-containing catecholamine neurons may not necessarily be adrenergic.

Psychiatric morbidity, platelet monoamine oxidase and tribulin output in headache

A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported.

Elevated Platelet MAO is Related to Impulsivity in Disruptive Behavior Disorders

Platelet monoamine oxidase (MAO) activity was measured in 32 drug-free prepubertal boys with externalizing symptoms of disruptive behavior disorders and 47 boys with no DSM-III-R diagnoses, and correlated to questionnaire and laboratory performance measures of impulsivity. A subgroup of boys with high MAO activity exhibited significantly poorer performance (i.e., more impulsivity) than a subgroup of low MAO activity on laboratory tasks requiring response inhibition. High MAO patients were more impulsive than high MAO controls on some performance tasks and elevated platelet MAO was unrelated to personality questionnaire measures of impulsivity or to patient status. These data suggest that biological markers such as MAO activity may correlate better with performance than clinical questionnaire measures. Abnormally high platelet MAO activity may not be sufficient to produce externalizing symptoms in children, perhaps interacting with an underlying behavioral dimension of impulsivity.

Platelet monoamine oxidase activity and life stress as predictors of psychopathology and coping in a community sample.

The present study, using a diathesis-stress model, attempted to confirm prior findings with platelet monoamine oxidase (MAO) activity and stress in a middle-aged, non-clinic population. One hundred and seventy-eight adult males from a statewide community club were tested for platelet MAO activity and stressful life events and were also given a variety of psychological measures of both psychopathology and psychosocial coping. The data were examined both for correlations across the total sample and for a comparison of high-risk groups (top and bottom 15% of MAO activity) with a middle MAO group. Low platelet MAO activity was related to a higher incidence of contact with mental health professionals, and more frequent use of alcohol and cigarette smoking. High MAO activity was related to higher levels of anxiety and somatization. High levels of stress were related to increased psychosocial problems reported for female and family members, higher scores on two schizophrenia-related MMPI scales (schizophrenia and paranoia subscales), but fewer idiosyncratic associations, elevated hypomanic, depression, and anxiety scores, increased alcohol use, and increased use of prescribed antianxiety and sedative medication. Neither MAO nor stress were related to current levels of psychosocial coping. Moreover, no interaction effects were uncovered for MAO activity and stress combined.

Changes in Serum Calcium, Magnesium, Cyclic AMP and Monoamine Oxidase Levels during Pregnancy and under Prolonged Ritodrine Treatment for Preterm Labor

Changes in serum levels of calcium, magnesium, cAMP and monoamine oxidase (MAO) activity throughout pregnancy and during prolonged treatment for preterm labor with ritodrine were studied. cAMP levels in the third trimester of pregnancy were found to be significantly high and postpartum MAO activity was significantly low. In cases of preterm labor, serum levels of calcium, magnesium and MAO activity were significantly low during the initial stage of ritodrine administration, then recovered after more than 1 week of treatment despite the fact that given doses and serum levels of ritodrine remained constant and that the serum level of cAMP was still high. These results suggested that a control mechanism for MAO activity during pregnancy might exist due to an increase in catecholamine and that the beta 2-effect of ritodrine induced a lowering in serum calcium and magnesium levels. However, some homeostatic mechanism to regulate the ions might come into play later on the mechanism of down-regulation of ritodrine.

Platelet MAO activity and the cortisol response to dexamethasone in major depression

Previous studies have sometimes found a positive relationship between platelet monoamine oxidase (MAO) activity and dexamethasone nonsuppression in depressed patients. To assess this relationship in more detail, we examined the association between these two biological variables in unmedicated depressed patients. A positive correlation between platelet MAO activity and 8:00 am serum cortisol levels following an overnight dexamethasone test (1 mg) was observed. The relationship between high and low platelet MAO activity (median split) and suppression of serum cortisol levels was also significant. These relationships were stronger in bipolar patients. Multiple regression revealed that postdexamethasone 8:00 am dexamethasone levels and platelet MAO activity were independent predictors of the 8:00 am cortisol levels following dexamethasone. The possibility that platelet MAO activity may be a peripheral marker of brain serotonergic activity which in turn may affect various aspects of the hypothalamo-pituitary-adrenal axis activity, is discussed. We also found that all nine depressed patients studied ⩾ 15 days after admission were suppressors. Platelet MAO activity, but not 8:00 am pre- or postdexamethasone serum cortisol, was related to the severity of depression.

Prediction of response to nortriptyline and phenelzine by platelet MAO activity.

Thirty-seven depressed patients over the age of 55 were treated for 5-7 weeks with either nortriptyline, a tricyclic antidepressant, or phenelzine, a monoamine oxidase (MAO) inhibitor. Patients' platelet MAO activity was measured following a drug washout period before treatment. Patients with higher MAO activity had a better response to treatment, regardless of which drug was used.

Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET.

The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.

Personality Correlates of Platelet Monoamine Oxidase (MAO) Activity in Female and Male Subjects

Associations between platelet monoamine oxidase (MAO) activity and scale scores from the Eysenck Personality Questionnaire, the Impulsiveness-Venturesomeness-Empathy inventory and the Karolinska Scales of Personality were studied in 32 female and 29 male students (age range 17-19 years). There were significant negative correlations between MAO activity and extraversion-related scales for male subjects; in the female group the correlations were also negative but nonsignificant. When comparing subgroups with low, intermediate, and high platelet MAO activity subjects, consistent trends were observed in the direction of higher scores in the impulsivity scales, the sensation seeking-related Monotony avoidance scale, and the Indirect Aggression scale for both female and male low MAO activity groups.

The dexamethasone suppression test (DST) and platelet monoamine oxidase (MAO) activity as predictors of psychosis in depression

The Dexamethasone Suppression Test (DST) has been used extensively to identify patients with endogenous and/or melancholic depressions. Moreover, patients with psychotic forms of endogenous depression have been found to be more likely to have abnormal DSTs than are patients with nonpsychotic forms of these depressions (Carroll et al. 1980; Coryell et al. 1982; Rudorfer et al. 1982; Caroff et al. 1983; Evans et al. 1983; Schatzberg et al. 1983a). Focusing on the specific values of 4:00 PM postdexamethasone serum cortisol levels, rather than simply on the qualitative distinction between suppression and nonsuppression, Schatzberg et al. (1983a) showed that depressed subjects with very high cortisol levels tend to be psychotic. For example, in patients with major depression, they found psychosis in over 70% (7/9) of the patients with postdexamethasone cortisol levels over 15 kg/dl, but in less than 20% (7/36) of the patients with postdexamethasone cortisol levels less than 15 p,g/dl. Platelet monoamine oxidase (MAO) activity has also been widely studied in affective illness. Findings by Meltzer et al. (1980) and by Schildkraut et al. (1977) suggest that high platelet MAO activity might be associated with psychotic depression. particularly in female patients. Furthermore, Schatzberg et al. (1983b) found a significant association between high platelet MAO activity (37.0 nmol tryptamine deaminatedlhrimg protein) and DST nonsuppression in depressed patients. Given the apparent relationship between DST nonsuppression and psychosis in depressed patients. these findings of Schatzberg ct al. would be compatible with an association between high platelet MAO activity and psychotic depression. In the following case report. the authors suggest that the combination ot‘ an extremely