Monoamine Oxidases: From Tissue Homogenates to Transgenic Mice

Shih, Jean C.

doi:10.1007/s11064-007-9384-z

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…Recently, an additional mitochondrial protein, monoamine oxidase (MAO), is emerging as a major ROS source with potential pathophysiological relevance [2, 3]. MAO is an ubiquitously expressed FAD-dependent enzyme localized at the outer mitochondrial membrane that exists in two isoforms, MAO-A and B, with peculiar tissue distribution, substrate selectivity, and inhibitor specificity [4]. MAO-A substrates include noradrenaline (NE) and serotonin (5-HT), while phenylethylamine is a specific substrate of MAO-B.…”

Section: Introductionmentioning

confidence: 99%

Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

Manni

Rigacci

Borchi

et al. 2016

Oxidative Medicine and Cellular Longevity

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Growing evidence indicates that reactive oxygen species (ROS) may play a key role in human heart failure (HF). Monoamine oxidase (MAO) is emerging as a major ROS source in several cardiomyopathies. However, little is known about MAO activity in human failing heart and its relationship with redox imbalance. Therefore, we measured MAO activity in the left (LV) and in the right (RV) ventricle of human nonfailing (NF) and in end-stage ischemic (IHD) and nonischemic failing hearts. We found that both MAO isoforms (MAO-A/B) significantly increased in terms of activity and expression levels only in IHD ventricles. Catalase and aldehyde dehydrogenase-2 activities (ALDH-2), both implicated in MAO-catalyzed catecholamine catabolism, were significantly elevated in the failing LV, whereas, in the RV, statistical significance was observed only for ALDH-2. Oxidative stress markers levels were significantly increased only in the failing RV. Actin oxidation was significantly elevated in both failing ventricles and related to MAO-A activity and to functional parameters. These data suggest a close association between MAO-A-dependent ROS generation, actin oxidation, and ventricular dysfunction. This latter finding points to a possible pathogenic role of MAO-A in human myocardial failure supporting the idea that MAO-A could be a new therapeutic target in HF.

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Section: Introductionmentioning

confidence: 99%

Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

Manni

Rigacci

Borchi

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…Monoamine oxidases (MAOs) 2 are catalytically active flavoproteins that are widely expressed in the animal kingdom (1). They catalyze the oxidation of endogenous and xenobiotic amines to the corresponding aldehydes.…”

mentioning

confidence: 99%

Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis

Wang

Borchert

Ugun-Klusek

et al. 2011

Journal of Biological Chemistry

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Monoamine oxidases (MAO-A, MAO-B) metabolize biogenic amines and have been implicated in neuronal apoptosis. Although apoptosis is an important process in embryo development, the role of MAO isoenzymes has not been investigated in detail. We found that expression of MAO-A and MAO-B can be detected early on during embryo development. Expression levels remained constant until around midgestation but then dropped to almost undetectable levels toward birth. Similar expression kinetics were observed in the brain. Isoform-specific expression silencing of MAO-A mediated by siRNA during in vitro embryogenesis induced developmental defects, as indicated by a reduction of the crown rump length and impaired cerebral development. These alterations were paralleled by elevated serotonin levels. Similar abnormalities were observed when embryos were cultured in the presence of the MAO-A inhibitor clorgyline or when the transcriptional inhibitor of MAO-A expression R1 was overexpressed. In contrast, no such alterations were detected when expression of MAO-B was knocked down. To explore the underlying mechanisms for the developmental abnormalities in MAO-A knockdown embryos, we quantified the degree of developmental apoptosis in the developing brain. MAO-A knockdown reduced the number of apoptotic cells in the neuroepithelium, which coincided with impaired activation of caspases 3 and 9. Moreover, we observed reduced cyclin D1 levels as an indicator of impaired cell proliferation in MAO-A knockdown embryos. This data highlights MAO-A as a vital regulator of embryonic brain development.

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“…The length of both genes amounts to 60 to 70 kb, both are composed of an equal number of exons (n=15) and both have the same exon and intron organization, suggesting that they have emerged by duplication of the same progenitor gene. Both MAO amino acid sequences in humans and rats show 88% conformity 72 . Significant differences between MAO-A and MAO-B genes exist in transcription elements in promoter organizations and precisely these differences are responsible for various tissue and cell expression of individual enzyme, especially when bound to the catecholaminergic and serotonergic brain neurons 70,73 .…”

Section: Mao-a and Mao-b Gene Structurementioning

confidence: 98%

“…Isoenzymes A and B are composed of 527 and 520 amino acids, their molecular mass is 59700 and 58000, respectively, and they show 70% of identical amino acid sequences. Both sequences contain pentapeptide Ser-Gly-Gly-Cy-Tyr covalently connected to the coenzyme flavin adenine dinucleotide (FAD) 72 . The primary structure of both MAO isoenzymes consists of three regions, i.e.…”

Section: Isoenzyme Mao-a and Mao-b Structurementioning

confidence: 99%

Neurobiological Bases of Alcohol Addiction

Matošić¹,

Marušić²,

Vidrih³

et al. 2016

ACC

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SUMMARY -Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter a...

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Monoamine Oxidases: From Tissue Homogenates to Transgenic Mice

Cited by 9 publications

References 34 publications

Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis

Neurobiological Bases of Alcohol Addiction

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