Immunological uniqueness of human monoamine oxidases A and B: new evidence from studies with monoclonal antibodies to human monoamine oxidase A

Kochersperger, LM; Waguespack, Ann; Patterson, JC; Cc, Hsieh; Weyler, Walter; Salach, James I.; Denney, R M

doi:10.1523/jneurosci.05-11-02874.1985

Cited by 54 publications

(14 citation statements)

References 21 publications

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“…The 3rd series of all cases (except for those of cases 6, 11 and 15: table 1) was reacted with a monoclonal anti-human NGFr antibody [44] at a dilu tion of 1:2,000 in 1 % NGS in PBS. For the 4th series (cases 1-3, 7-11 and 13-15; table 1), a polyclonal mouse anti-human placental MAO A antibody [45] was used at a dilution of 1:20,000 in 1 % NGS in PBS. After a 4-day incubation at 4 0 C the sections were reacted with a gold-labeled secondary antibody at a dilution of 1:400 in 1 % NGS in PBS for 24 h. The visualization was performed with a silver enhancement method described earlier [46].…”

Section: Fixation and Immunocytochemistrymentioning

confidence: 99%

Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

Chan‐Palay¹,

Höchli²,

Savaskan³

et al. 1993

Dement Geriatr Cogn Disord

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In this study, calbindin D-28k (CaBP), monoamine oxidase A (MAO A) and nerve growth factor receptor (NGFr) immunoreactivities were investigated in the nucleus basalis of Meynert (NbM) in patients with senile dementia of the Alzheimer type (SDAT), with Parkinson''s disease (PD) with or without dementia, and in controls. Immunocytochemistry using specific antibodies in differing serial sections was employed, and cell counts and NbM nuclear volume measurements were made. Most of the large multipolar NbM neurons showed CaBP immunoreactivity in the cytoplasm of their somata, dendrites and axons. In adjacent, NGFr-reacted sections, the large NbM neurons were also found to be intensely immunoreactive for NGFr on their cellular surfaces. In addition, a subpopulation of large NbM neurons and glial cells were found to be immunoreactive for MAO A. The number of CaBP-immunoreactive (CaBP-i) neurons was decreased by an average of 55% in the 6 SDAT patients, 70% in the 2 nondemented PD patients and 40% in the 1 demented PD patient. The volume calculated for the compact part of the NbM formed by the CaBP-i neuronal somata decreased by an average of 47% in SDAT. On the other hand, measurements in the volume of NGFr-i neurons (including the dendritic arborization) showed an average decrease of 25% in SDAT patients compared to controls. Although all SDAT and PD patients showed a decrease of CaBP-i neurons in the NbM, a loss of MAO-A-i NbM neurons was found only in those patients with dementia. Therefore, the relative proportions of MAO-A-i to CaBP-i neurons were increased in the nondemented PD patients (14.2 and 19.6%) when compared with those in the demented PD patient (2.2%) and with the SDAT patients (0.3-5.6%). These data indicate that a balanced presence of MAO-A-i cholinergic, large NbM neurons may be necessary for the proper maintenance of cognitive function. Functionally this may be translated to mean that dementing changes may cause a decrease from the normal amount of MAO A enzyme activity. This suggests that therapeutic strategies based upon correction of MAO-A activities by MAO-A inhibitors may be important to ameliorating some of the loss in cholinergic function in dementias of SDAT and PD.

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Section: Fixation and Immunocytochemistrymentioning

confidence: 99%

Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

Chan‐Palay¹,

Höchli²,

Savaskan³

et al. 1993

Dement Geriatr Cogn Disord

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“…These enzymes, which are integral proteins of the outer mitochondrial membrane (4), are distinguished by differences in substrate preference (5), inhibitor specificity (6), tissue and cell distribution (7), and immunological properties (8,9). MAO A preferentially oxidizes the biogenic amine serotonin and is inactivated irreversibly by the acetylenic inhibitor clorgyline.…”

Section: Introductionmentioning

confidence: 99%

cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties.

Bach

Lan

Johnson

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

660

411

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The monoamine oxidases play a vital role in the metabolism of biogenic amines in the central nervous system and in peripheral tissues. Using oligonucleotide probes derived from three sequenced peptide fragments, we have isolated cDNA clones that encode the A and B forms of monoamine oxidase and have determined the nucleotide sequences of these cDNAs. Comparison of the deduced amino acid sequences shows that the A and B forms have subunit molecular weights of 59,700 and 58,800, respectively, and have 70% sequence identity. Both sequences contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, in which the obligatory cofactor FAD is covalently bound to cysteine. Based on differences in primary amino acid sequences and RNA gel blot analysis of mRNAs, the A and B forms of monoamine oxidase appear to be derived from separate genes.Monoamine oxidases A and B [MAO A and MAO B, respectively; amine:oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4] in the central nervous system and in peripheral tissues catalyze the oxidative deamination of neuroactive and vasoactive amines (1) and the oxidation of xenobiotics, including the parkinsonism-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2, 3). These enzymes, which are integral proteins of the outer mitochondrial membrane (4), are distinguished by differences in substrate preference (5), inhibitor specificity (6), tissue and cell distribution (7), and immunological properties (8,9). MAO A preferentially oxidizes the biogenic amine serotonin and is inactivated irreversibly by the acetylenic inhibitor clorgyline. MAO B preferentially oxidizes phenylethylamine and benzylamine and is inactivated by the irreversible inhibitors pargyline and deprenyl. The level of MAO activity in almost all human tissues consists of a mixture of both forms of the enzyme, but placental tissue contains predominantly MAO A (10), whereas platelets and lymphocytes express only MAO B (11,12). MAO A and B from several tissue sources and species appear to consist of two subunits with approximate molecular masses of 60 kDa (13,14 (15,19). Peptide maps obtained from proteinase digestion of [3H]pargyline-labeled crude or partially purified MAO A and B suggest that these enzymes differ in their amino acid sequences (17,20). Furthermore, differences in degrees of photo-dependent inactivation of these two enzymes suggest the existence of conformational or structural differences in their active sites (21-23).To clarify the molecular basis of structural and functional differences between these important enzymes, we have isolated and characterized cloned cDNAsI encoding these proteins. The nucleotide and deduced amino acid sequences for human liver MAO A and B show that these two proteins are derived from separate genes. MATERIALS AND METHODSConstruction and Screening of the Human Liver cDNA Library. A Agt1O library was constructed from poly(A)+ mRNA isolated from human liver (24). The phage library contained 2 x 106 individual clones of which 5 x 105 clones were subjected to hy...

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“…These isozymes are integral proteins of the outer mitochondrial membrane (1) and can be distinguished by differences in substrate preference (2), inhibitory specificity (3), tissue and cell distribution (4 -6), and immunological properties (7)(8)(9). Furthermore, comparison of their nucleotide and deduced amino acid sequences show that human MAO A and B are two distinct proteins encoded by different genes (10).…”

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confidence: 99%

Flavinylation of Monoamine Oxidase B

Zhou

Lewis

Kwan

et al. 1995

Journal of Biological Chemistry

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Monoamine oxidase B (MAO B)The major amine-degrading enzymes in the central nervous system and peripheral tissues of mammals are monoamine oxidase A and B (MAO 1 A and B, amine:oxygen, oxidoreductase (deaminating, flavin-containing), EC 1.4.3.4). These isozymes are integral proteins of the outer mitochondrial membrane (1) and can be distinguished by differences in substrate preference (2), inhibitory specificity (3), tissue and cell distribution (4 -6), and immunological properties (7-9). Furthermore, comparison of their nucleotide and deduced amino acid sequences show that human MAO A and B are two distinct proteins encoded by different genes (10).Oxidation of amines by MAO is coupled to the reduction of an obligatory cofactor, FAD, which is covalently linked to the enzyme. Five types of bonds are generally found in the covalent linkage of flavins to their respective apoproteins (11). These include a histidine residue which can be attached through its N-1 or N-3 atom to the 8␣-methyl group of the isoalloxazine ring to form a tertiary amine; a cysteine residue which forms a thioether linkage with either the 8␣-methyl group or the C-6 of the xylene ring of the flavin molecule; or a tyrosine residue can become linked to the 8␣-methyl group to form an (O)-8␣-flavin bond. In MAO A and B, the 8␣-methyl group of FAD is bound covalently to cysteine through a thioether linkage in the pentapeptide SGGCY (12, 13). Comparison of this segment with the complete deduced amino acid sequences of MAO A and B indicated that FAD is covalently bound to Cys 406 in MAO A and Cys 397 in MAO B, respectively (10). In addition, site-directed mutagenesis studies of MAO B, where Cys 397 was substituted with serine or histidine, showed that this cysteine residue is essential for catalytic activity (14,15).Although the amino acid sequences surrounding the FAD covalent attachment site in different flavoproteins bear little homology, a distinct non-covalent FAD-binding site displays high sequence identity in many FAD-containing enzymes of diverse function (16,17). This non-covalent FAD binding region is commonly referred to as the dinucleotide-binding site or motif due to its interaction with the AMP moiety of FAD. This motif consists of a ␤ 1 -sheet-␣-helix-␤ 2 -sheet beginning with a highly conserved Gly-X-Gly-X-X-Gly sequence between the first ␤-sheet and the ␣-helix. The second ␤-sheet usually ends with a glutamate residue in which the ␥-carboxylate group is thought to interact through a hydrogen bond with the 2Ј-hydroxyl group of ribose in the AMP moiety of FAD. In MAO A and B, this motif is located at the N terminus of MAO A (residues 15-43) and MAO B (residues 6 -34) and ends in Glu 43 and Glu 34 , respectively. Site-directed mutagenesis studies, where Glu 34 was replaced with aspartate, glutamine, or alanine, resulted in near complete or total loss of catalytic activity in MAO B (18).A fundamental process in the intracellular generation of functional flavoenzymes is the molecular mechanism which generates holoenzyme from apoenzyme a...

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Immunological uniqueness of human monoamine oxidases A and B: new evidence from studies with monoclonal antibodies to human monoamine oxidase A

Abstract: Monoamine oxidase (EC 1

Cited by 54 publications

References 21 publications

Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties.

Flavinylation of Monoamine Oxidase B

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