Disease relevance of Maoa

• The data of [3H]harman displacement support the hypothesis of a high-affinity binding site of the neurotoxin MPP+ located on mitochondrial MAO-A with a significant influence on the development of MPTP induced parkinsonism [1].
• Administration of MAO-A inhibitors during ischemia was still effective in preventing cardiac damage [2].
• MAO-B inhibitors (pargyline [55%], deprenyl [43%]) but not MAO-A inhibitors (clorgyline [91%]) significantly decreased the frequency of duodenal ulcers suggesting that, like MPTP-induced parkinsonism, formation of a toxic metabolite, probably 1-methyl-4-phenyl-pyridinium is involved [3].
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced toxicity in PC12 cells: role of monoamine oxidase A [4].
• PC 12 cells also contained predominantly MAO-A (90%); however, an increased Km for phenylethylamine and a sensitivity of deamination of this MAO-B substrate to inhibition by clorgyline are indicators of abnormal behavior of MAO in this clonal rat pheochromocytoma cell line [5].

Psychiatry related information on Maoa

• As selective MAO-A and MAO-B inhibition may be effective in different depressive subtypes and may have different side effects, these drugs are valuable pharmacologic probes for studying the biochemical bases of depressive disorders [6].
• Monoamine oxidase, monoamine oxidase-A, and monoamine oxidase-B activities were compared in free moving, rapid eye movement sleep-deprived, recovered, and control rat brains [7].
• Medullary MAO-A was the first to be affected, showing an increase after just one day of rapid eye movement sleep deprivation, while longer deprivation decreased its activity [7].
• MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise [8].
• Therefore we used the histochemical approach for examination of the effect of chronic alcohol consumption on MAO A and B activities in definite brain structures: various types of aminergic neurons, glial cells and blood capillaries [9].

High impact information on Maoa

• Monoamine oxidase A and B (MAO A and B) are the major neurotransmitter-degrading enzymes in the central nervous system and in peripheral tissues [10].
• MAO A and B cDNAs from human, rat, and bovine species have been cloned and their deduced amino acid sequences compared [10].
• The genes that encode MAO A and B are closely aligned on the X chromosome (Xp11.23), and have identical exon-intron organization [10].
• MAO-A is also undetectable in neurons containing 5-HT, a good substrate for MAO-A [11].
• Furthermore, although the inhibition of DA reuptake by cocaine and nomifensine caused a short-term prolongation of DA responses, the combined inhibition of MAO A and B enzymes caused a long-term prolongation of DA effects [12].

Chemical compound and disease context of Maoa

• BACKGROUND: Serotonin (5-hydroxytryptamine [5-HT]), released by activated platelets during cardiac ischemia, is metabolized by the mitochondrial enzyme monoamine oxidase A (MAO-A) [2].
• Replacement therapy with T3 did not normalize MAO-A activity in hypothyroidism [13].
• These data are consistent with the concept that the MAO-A-dependent formation of the pyridinium species from the tetrahydropyridine is a prerequisite for toxicity in PC12 cells [4].
• The data thus suggest that selective MAO-A inhibitors such as esuprone may be an interesting new approach for the treatment of epilepsy [14].
• [3H]Pargyline was bound to MAO A and B in a crude mitochondrial fraction from rat hepatoma cell line MH1C1 and to MAO A in a mitochondrial fraction from rat glioma line C6 [15].

Biological context of Maoa

• Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling [16].
• A three-dimensional quantitative structure-activity relationship study for MAO-A inhibition was performed on the series using comparative molecular field analysis (CoMFA) [16].
• Clorgyline, a monoamine oxidase-A (MAO-A) inhibitor, did not protect NGF-differentiated PC12 cells against OGD-induced cell death [17].
• The results of this study show that epinine is a substrate for both forms of MAO in rat liver, although the contribution of MAO A to the deamination of this secondary amine appears to be slightly more important than that of MAO B [18].
• Displacement of the [3H]pargyline binding on MAO-A (L(-)-deprenyl suppressed binding to MAO-B) by harman, 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) revealed IC50 values of 250 +/- 100 nM, 3.1 +/- 0.8 microM, and 5.1 +/- 0.4 microM, respectively [1].

Anatomical context of Maoa

• Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors [19].
• The in vitro binding of [3H]pargyline and [3H]harman ([3H]1-methyl-beta-carboline) to monoamine oxidase A (MAO-A; EC 1.4.3.4) on membranes of rat cerebral cortex was evaluated [1].
• In contrast styrene monomer slightly inhibited both MAO-A and MAO-B activities in rat brain mitochondria [20].
• The deamination of [14C]noradrenaline within the noradrenergic synaptosomes from the hypothalamus and that of [14C]dopamine and [14C]tyramine within the striatal dopaminergic synaptosomes were due to MAO-A [21].
• Intracerebroventricular injections of angiotensin II caused 108, 62, and 54% increases in monoamine oxidase A activities in rat hippocampus, hypothalamus, and striatum, respectively [22].

Associations of Maoa with chemical compounds

• Clorgyline inhibited MAO-A by 95%, with 30% inhibition of MAO-B [23].
• These results show for the first time the existence of a dopamine-dependent MAO-A regulation involving D(2)-like receptors, inhibition of the cAMP-PKA pathway, and an ex novo enzyme synthesis [19].
• Chronic treatment with the MAO-B inhibitors reduced striatal MAO-B activity by 90%, with 15% (TVP-1012) or 40% (deprenyl) inhibition of MAO-A [23].
• Thus, while most of the condensed pyridazines were reversible inhibitors of MAO-B with little or no MAO-A effects, the pyrimidine derivatives proved to be reversible and selective MAO-A inhibitors [24].
• The increase in MAO-A protein was preceded by an augmentation of MAO-A mRNA that was prevented by the transcriptional inhibitor actinomycin D [19].

Physical interactions of Maoa

• A relatively high density of [3H]RO41-1049 binding to MAO-A enzyme was present in all regions of the rat kidney (160-210 fmol/mg) compared with a low density of [3H]RO19-6327 binding to MAO-B (< 25 fmol/mg) [25].

Regulatory relationships of Maoa

• MAO B was markedly inhibited with the oral dose of 1 mg/kg without any alteration of MAO A, and the inhibition almost did not exceed 24 h [26].

Other interactions of Maoa

• A single mutation in which Phe-208 in MAO A was substituted by the corresponding residue of Ile in MAO B was sufficient to convert the A-type substrate selectivity, and the reverse was exactly the case [27].

Analytical, diagnostic and therapeutic context of Maoa

• Crystallization and preliminary crystallographic analysis of rat monoamine oxidase A complexed with clorgyline [28].
• 5. MAO-A inhibitory properties on tuberculum olfactorium and striatum could be of interest according to some animal models of depression [29].
• We have synthesized N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropar gylamine (18F-fluoroclorgyline) as a potential positron emission tomography (PET) radiotracer for monoamine oxidase A (MAO-A) [30].
• The RT-PCR products for both MAO-A and MAO-B, were found to have the expected sizes [31].
• In vivo, inhibition of MAO-A largely reduced myocardial ultrastructural damage induced by 30 minutes of ischemia followed by 60 minutes of reperfusion in the rat heart [2].

References