Monoamine Oxidases, Oxidative Stress, and Altered Mitochondrial Dynamics in Cardiac Ageing

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3017947 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 28

Author(s):

Damien Maggiorani ◽

Nicola Manzella ◽

Dale E. Edmondson ◽

Andrea Mattevi ◽

Angelo Parini ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Scientific Evidence ◽

Mitochondrial Enzymes ◽

Oxidative Deamination ◽

Monoamine Oxidases ◽

Mao B ◽

The Past ◽

Age Dependent ◽

Mao A

The advances in healthcare over the past several decades have resulted in populations now living longer. With this increase in longevity, a wider prevalence of cardiovascular diseases is more common and known to be a major factor in rising healthcare costs. A wealth of scientific evidence has implicated cell senescence as an important component in the etiology of these age-dependent pathologies. A number of studies indicate that an excess of reactive oxygen species (ROS) contributes to trigger and accelerate the cardiac senescence processes, and a new role of monoamine oxidases, MAO-A and MAO-B, is emerging in this context. These mitochondrial enzymes regulate the level of catecholamines and serotonin by catalyzing their oxidative deamination in the heart. MAOs’ expression substantially increases with ageing (6-fold MAO-A in the heart and 4-fold MAO-B in neuronal tissue), and their involvement in cardiac diseases is supposedly related to the formation of ROS, via the hydrogen peroxide produced during the substrate degradation. Here, we will review the most recent advances in this field and describe why MAOs could be effective targets in order to prevent age-associated cardiovascular disease.

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Multifunctional Monoamine Oxidases and Cholinesterases Inhibitory Effects, as well as UPLC-DAD-MS Chemical Profile of Alkaloid Fractions Obtained from Species of the Palicoureeae Tribe

Natural Product Communications ◽

10.1177/1934578x1601100920 ◽

2016 ◽

Vol 11 (9) ◽

pp. 1934578X1601100 ◽

Cited By ~ 2

Author(s):

Luiz Carlos Klein-Júnior ◽

Carolina dos Santos Passos ◽

Juliana Salton ◽

Fernanda Gobbi Bitencourt de ◽

Luís Funez ◽

...

Keyword(s):

Indole Alkaloids ◽

The Other ◽

Chemical Profile ◽

Inhibitory Effects ◽

Pharmacological Activities ◽

Monoamine Oxidases ◽

Mao B ◽

Bche Activity ◽

Neuropsychiatric Diseases ◽

Mao A

In the present study, the effects were evaluated of alkaloid fractions (AFs) from Psychotria species and correlated genera, Palicourea and Rudgea, on monoamine oxidases (MAOs) and cholinesterases (ChEs). By HPLC-DAD and UPLC-DAD-MS analyses, indole alkaloids (IA) were detected in all AFs. For the Psychotria and Palicourea species, these IA corresponded to tetrahydro-β-carboline alkaloids (THβCA). On the other hand, pyrrolidinoindoline core compounds were observed for Rudgea species. Regarding their pharmacological activities, none of the AFs was able to inhibit AChE. However, the BChE activity was impaired by the Psychotria and Palicourea AFs. In addition, MAO-A was inhibited by both AFs, but only Psychotria nemorosa AF was able to inhibit significantly MAO-B. Rudgea AFs demonstrated a poor inhibitory profile on MAO-A. Taken together, our results highlighted the Psychotria and Palicourea genera as important sources of scaffolds for the development of MAO-A and BChE inhibitors aiming at the treatment of neurodegenerative and neuropsychiatric diseases.

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Stereospecific deuterium substitution at the α-carbon position of dopamine and its effect on oxidative deamination catalyzed by MAO-A and MAO-B from different tissues

Biochemical Pharmacology ◽

10.1016/0006-2952(86)90094-8 ◽

1986 ◽

Vol 35 (6) ◽

pp. 1027-1036 ◽

Cited By ~ 43

Author(s):

Peter H. Yu ◽

Bruce A. Bailey ◽

David A. Durden ◽

Alan A. Boulton

Keyword(s):

Oxidative Deamination ◽

Mao B ◽

Deuterium Substitution ◽

Mao A ◽

Different Tissues

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Age-dependent alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain ? potential role of L-Carnitine

Biogerontology ◽

10.1007/s10522-004-2575-y ◽

2004 ◽

Vol 5 (5) ◽

pp. 355-364 ◽

Cited By ~ 21

Author(s):

Dayalan Haripriya ◽

Muthuswamy Anusuya Devi ◽

Vedagiri Kokilavani ◽

Purushotham Sangeetha ◽

Chinnakannu Panneerselvam

Keyword(s):

Rat Brain ◽

Potential Role ◽

Mitochondrial Enzymes ◽

Brain Potential ◽

Age Dependent

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From warrior genes to translational solutions: novel insights into monoamine oxidases (MAOs) and aggression

Translational Psychiatry ◽

10.1038/s41398-021-01257-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alexios-Fotios A. Mentis ◽

Efthimios Dardiotis ◽

Eleni Katsouni ◽

George P. Chrousos

Keyword(s):

Aggressive Behavior ◽

Noncoding Rna ◽

Integrated Approach ◽

Brain Areas ◽

Monoamine Oxidases ◽

The Past ◽

Collective Effort ◽

Novel Biomarkers ◽

Clinical Populations

AbstractThe pervasive and frequently devastating nature of aggressive behavior calls for a collective effort to understand its psychosocial and neurobiological underpinnings. Regarding the latter, diverse brain areas, neural networks, neurotransmitters, hormones, and candidate genes have been associated with antisocial and aggressive behavior in humans and animals. This review focuses on the role of monoamine oxidases (MAOs) and the genes coding for them, in the modulation of aggression. During the past 20 years, a substantial number of studies using both pharmacological and genetic approaches have linked the MAO system with aggressive and impulsive behaviors in healthy and clinical populations, including the recent discovery of MAALIN, a long noncoding RNA (lncRNA) regulating the MAO-A gene in the human brain. Here, we first provide an overview of the MAOs and their physiological functions, we then summarize recent key findings linking MAO-related enzymatic and gene activity and aggressive behavior, and, finally, we offer novel insights into the mechanisms underlying this association. Using the existing experimental evidence as a foundation, we discuss the translational implications of these findings in clinical practice and highlight what we believe are outstanding conceptual and methodological questions in the field. Ultimately, we propose that unraveling the specific role of MAO in aggression requires an integrated approach, where this question is pursued by combining psychological, radiological, and genetic/genomic assessments. The translational benefits of such an approach include the discovery of novel biomarkers of aggression and targeting the MAO system to modulate pathological aggression in clinical populations.

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Monoamine oxidase inhibition improves vascular function in mammary arteries from nondiabetic and diabetic patients with coronary heart disease

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0580 ◽

2016 ◽

Vol 94 (10) ◽

pp. 1040-1047 ◽

Cited By ~ 10

Author(s):

Rodica Lighezan ◽

Adrian Sturza ◽

Oana M. Duicu ◽

Raluca A. Ceausu ◽

Adrian Vaduva ◽

...

Keyword(s):

Oxidative Stress ◽

Coronary Heart Disease ◽

Heart Disease ◽

Coronary Artery ◽

Diabetic Patients ◽

Organ Bath ◽

Mitochondrial Enzymes ◽

Mao B ◽

Mammary Arteries ◽

Mao A

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H2O2 contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments. Clorgyline (irreversible MAO-A inhibitor), selegiline (irreversible MAO-B inhibitor), and moclobemide (reversible MAO-A inhibitor) were applied in the organ bath (10 μmol/L). MAO expression was assessed by immunohistochemistry. We found a constant impairment of EDR that has been significantly attenuated in the presence of the MAO-A and MAO-B inhibitors in both groups of coronary heart disease patients. MAO-B was the dominant isoform in all human diseased vessels. In conclusion, in vitro inhibition of MAO significantly improved EDR in human mammary arteries, regardless of the presence of diabetes. These data suggest that MAO inhibitors might be useful in restoring endothelial response in clinical conditions associated with increased oxidative stress, such as coronary artery disease and diabetes.

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A HISTORICAL ACCOUNT OF THE ROLE OF EXERCISE IN THE PREVENTION AND TREATMENT OF CANCER-RELATED LYMPHEDEMA

Lymphology ◽

10.2458/lymph.4655 ◽

2020 ◽

Vol 53 (2) ◽

Author(s):

K Johansson ◽

S Hayes

Keyword(s):

Lymphatic System ◽

Scientific Evidence ◽

Physical Activities ◽

High Load ◽

Historical Account ◽

Management Guidelines ◽

The Past ◽

Diagnosis Of Cancer

In the absence of guidance from scientific evidence, a range of lymphedema prevention and management, guidelines were developed by relevant organizations around the world. These became publicly available, promoted and endorsed, particularly to women with breast cancer. The recommendations advised avoidance of any activity that could overload or restrict the lymphatic system and need for caution when participating in specific physical activities. However, over the past 20 years evidence has accumulated which has significantly challenged the safety of these recommendations, in particular for those with cancer. There now exists consistent and compelling evidence in support of exercise following a diagnosis of cancer. Participating in exercise during and following cancer treatment improves function and quality of life, reduces treatment-related morbidity, and may improve survival. Further, exercise, including resistance exercise at moderate or high load, is considered safe for those at risk- or with lymphedema. That is, exercise has not been shown to cause or worsen cancer-related lymphedema. This article provides a historical account of the advice given to patients in the prevention and management of lymphedema and how this advice has evolved.

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Synthesis of N′-(4-/3-/2-/Non-substituted benzylidene)-4-[(4-methylphenyl)sulfonyloxy] Benzohydrazides and Evaluation of Their Inhibitory Activities against Monoamine Oxidases and β-Secretase

Applied Sciences ◽

10.3390/app11135830 ◽

2021 ◽

Vol 11 (13) ◽

pp. 5830

Author(s):

Hasan Erdinç Sellitepe ◽

Jong Min Oh ◽

İnci Selin Doğan ◽

Sercan Yildirim ◽

Ahmet Buğra Aksel ◽

...

Keyword(s):

Inhibitory Activity ◽

Potent Inhibitor ◽

Residual Activity ◽

Docking Studies ◽

Monoamine Oxidases ◽

Mao B ◽

Ic50 Value ◽

Mao A ◽

Inhibitory Activities ◽

Bace 1

Nineteen tosylated acyl hydrazone derivatives were synthesized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 3o was the most potent inhibitor of MAO-A, with an IC50 value of 1.54 µM, followed by 3a (IC50 = 3.35 µM). A structural comparison with 3a indicated that the 3-F group in 3o increased its inhibitory activity against MAO-A. Compound 3s was the most potent inhibitor of MAO-B, with an IC50 value of 3.64 µM, followed by 3t (IC50 = 5.69 µM). The MAO-B inhibitory activity increased in the order of 3- > 4- > 2-NO2 groups in 3s, 3t, and 3r, respectively. All the compounds weakly inhibited AChE and BChE, which retained >50% residual activity at 10 µM, except for 3a, which inhibited BChE with an IC50 value of 16.1 µM. Interestingly, 3e, 3f, and 3n inhibited BACE-1 with IC50 values of 8.63, 9.92, and 8.47 µM, respectively, which were lower than the IC50 of the quercetin reference. Compounds 3o and 3s were found to be reversible competitive inhibitors of MAO-A and MAO-B, respectively, with Ki values of 0.35 ± 0.074 and 1.97 ± 0.65 µM, respectively. Moreover, compounds 3e, 3f, and 3n were effective BACE-1 inhibitors. The lead molecules were further investigated by molecular docking studies to elucidate the binding interactions with the target enzymes.

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Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

Pharmaceuticals ◽

10.3390/ph14050398 ◽

2021 ◽

Vol 14 (5) ◽

pp. 398

Author(s):

Narayan D. Chaurasiya ◽

Haining Liu ◽

Robert J. Doerksen ◽

N. P. Dhammika Nanayakkara ◽

Larry A. Walker ◽

...

Keyword(s):

Enzyme Inhibitor ◽

Pneumocystis Pneumonia ◽

Clinical Development ◽

Radical Cure ◽

Inhibitor Binding ◽

Strong Inhibitor ◽

Computational Docking ◽

Monoamine Oxidases ◽

Mao B ◽

Mao A

8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(−) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(−)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(−) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.

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Immunocytochemical localization of monoamine oxidases A and B in human peripheral tissues and brain.

Journal of Histochemistry & Cytochemistry ◽

10.1177/35.1.3025289 ◽

1987 ◽

Vol 35 (1) ◽

pp. 23-32 ◽

Cited By ~ 118

Author(s):

L W Thorpe ◽

K N Westlund ◽

L M Kochersperger ◽

C W Abell ◽

R M Denney

Keyword(s):

Hepatoma Cell ◽

Hepatoma Cell Line ◽

Human Hepatoma Cell ◽

Peripheral Tissues ◽

Monoamine Oxidases ◽

Mao B ◽

Mao A ◽

Immunocytochemical Techniques ◽

High Degree ◽

The Brain

Monoamine oxidases (MAO; EC 1.4.3.4.) A and B occur in the outer mitochondrial membrane and oxidize a number of important biogenic and xenobiotic amines. Monoclonal antibodies specific for human MAO A or B and immunocytochemical techniques were used to visualize the respective enzymes in human placenta, platelets, lymphocytes, liver, brain, and a human hepatoma cell line. MAO A was observed in the syncytiotrophoblast layer of term placenta, liver, and a subset of neurons in brain, but was not observed in platelets or lymphocytes, which are known to lack type A enzyme. MAO B was observed in platelets, lymphocytes, and liver, but not in placenta, which contains little or no MAO B. MAO B was also observed in a subset of neurons in the brain that was distinct from that which contained MAO A. MAO A and MAO B were also observed in some glia. Unlike most tissues examined, liver cells appeared to contain both forms of the enzyme. These studies show that MAO A and MAO B can be specifically visualized by immunocytochemical means in a variety of human cells and tissues and can provide a graphic demonstration of the high degree of cell specificity of expression of the two forms of the enzyme.

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