DOCSLIB.ORG

3. Monomine Oxidase Inal finding by a Replication Study in an Independent Ital- Ian Sample

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
3. Monomine Oxidase Inal finding by a Replication Study in an Independent Ital- Ian Sample Abstracts S96 229. ASSOCIATION BETWEEN ALLELIC VARIATION the U.K. blood transfusion service. Genotyping was done IN THE SEROTONIN TRANSPORTER GENE AND PER- on an ABI 373 DNA sequencer using the ABI GENESCAN VASIVE DEVELOPMENTAL DISORDER. 1Zwaigenbaum and GENOTYPER software. Patient and control data were L, 2Mejia J, 1Szatmari P, 2Palmour R, 3Jones MB, 2Paliouras analysed by CLUMP vs 1.1 and 2 × 2 contingency tables G, 1Bryson SE, 1Bartolucci G, 1Mahoney W.. 1Centre for were analysed by Pearson chi square test. Studies of Children at Risk, Department of Psychiatry, Alleles containing 3 and 4 repeats were most fre- McMaster University, Hamilton, Ontario; 2Department of quent, making up 35% and 62% of the sample respect- Human Genetics and Psychiatry, McGill University, Mon- ively. No significant differences were observed in allele treal, Quebec; 3Department of Behavioural Science, Penn frequency between patients and controls, p=0.188. When State, Hershey, Pennsylvania. the alleles were grouped into high and low expression, Serotonin has long been suggested to play a role in again no significant differences were observed, ␹2=1.81, the pathophysiology of autism/pervasive developmental p=0.25. Male and female data were also analysed separ- disorder (PDD). Cook and colleagues (1997) first reported ately (male, n=108; female, n=46), with no significant dif- an preliminary evidence of linkage and association ferences. between autism and the serotonin transporter (5HTT) gene (short variant of the second intron of the promoter region). Subsequent efforts have failed to replicate this finding, 1 Sabol et al. (1998): Hum Genet 103: 273–279 although one group has found preferential transmission of 2 Williams et al. (1998): Am J Med Genet (Neuropsychiatric Genet) the opposite (long) variant in a PDD sample (Klauck et al., 81: 453 1997). The purpose of this study is to further assess 5HTT 3 Norton et al. (1998): Am J Med Genet (Neuropsychiatric Genet) as a candidate gene in trios consisting of probands with 81: 529 PDD and both parents. We have collected DNA samples from 116 families for TDT analysis. Probands were diag- nosed with PDD by consensus best estimate. Preliminary analysis considreted on 76 families shows a non-signifi- 231. EXCESS OF LONG MONOAMINE OXIDASE A cant trend towards preferential transmission of the long GENE PROMOTER ALLELES IN FEMALE PATIENTS variant of the 5HTT promoter to PDD probands (TDT chi- = = = WITH PANIC DISORDER: FUNCTIONAL CHARAC- squared 2.13, d.f. 1, p 0.14). We will complete the TERIZATION AND REPLICATION. Deckert J, Catalano M, analysis on the entire sample, and assess for genetic het- Syagailo YV, Bosi M, Okladnova O, DiBella D, No¯then erogeneity on the basis on gender, I.Q., and PDD subtype MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, (autism vs. non-autism). Beckmann H, Bellodi L and Lesch KP.. Departments of Psychiatry, Universities of Wu¨ rzburg and Bonn, Institute Cook EH Jr, Courchesne R, Lord C et al. (1997). Evidence of linkage between the serotonin transporter and autistic disorder. Molecular of Human Genetics Bonn, Germany and IRCCS H San Raf- Psychiatry, 2, p247–250. faele Milan, Italy. Klauk SM, Poustka F, Benner A et al. (1997). Serotonin transporter Increased frequency of the longer of several monoam- gene variants associated with autism? Human Molecular Genetics, ine oxidase A gene promoter alleles has been observed 6, p2233–8. among female patients in a German sample (Am J Med Genet 81/6, 514, 1998). To probe the relevance of this observation we performed a functional characterization of the different promoter alleles and complemented the orig- 3. Monomine Oxidase inal finding by a replication study in an independent Ital- ian sample. Panic disorder was diagnosed according to DSMIII-R 230. NO EVIDENCE FOR ASSOCIATION BETWEEN using as interviews SADS-LA, CIDI and DIS-R (total n=209, 80 German and 129 Italian). Controls were of the SCHIZOPHRENIA AND MAO-A PROMOTER POLYMOR- = PHISM. Norton N,. Bray NJ, Williams NM, Cardno AC, same ethnic background (total n 190, 80 German and 110 Murphy KC, Jones LA, Sanders RD, McCarthy G, McGuffin Italian). Genotyping was performed as previously P, and Owen MJ.. Department of Psychological Medicine, described. In addition, functional characterization of the University of Wales College of Medicine, Heath Park, Car- different promoter alleles (3, 3a, 4 and 5 repeats) was per- diff, CF4 4XN. formed in SH-SY5Y cells by means of a luciferase assay. Monoamine Oxidase, (MAO-A), is a mitochondrial As in the German sample higher frequency of the longer enzyme which preferentially oxidizes serotonin and nore- alleles (3a, 4 and 5) and of genotypes containing only piniphrine. The gene encoding MAO-A maps to longer alleles was observed among females in the Italian = = Xp11.23–11.4. sample (p 0.01 and p 0.05 respectively). Combining the Sabol et al, 19981, reported a VNTR polymorphism two female subsamples increased significance to p=0.001 within the promoter of MAO-A, whereby alleles with 3.5 for the allele distribution and p=0.01 for the genotype dis- and 4 repeat elements produced a significantly higher tribution. Functional characterization demonstrated transcription rate than alleles containing 3 and 5 repeat approximately 50% higher activity of the longer alleles in elements as determined by gene fusion and transfection comparison with the short allele. experiments. MAO-A inhibitors are an effective treatment for Following the highest lod score of 1.6 in the region patients with panic disorder, in particular females. This Xp11 from our schizophrenia affected sib pair genome clinical observation is consistent with our finding that scan2,3, we tested for allelic association of the MAO-A homozygosity for monoamine oxidase A gene promoter VNTR polymorphism and schizophrenia. 154 caucasian, alleles with high expression of monoamine oxidase A may DMS-IV schizophrenia patients from the U.K. were age constitute a vulnerability factor in the pathogenesis of and sex matched with 154 control subjects collected from panic disorder. Abstracts S97 232. GENOTYPE OF THE MAO A PROMOTER-ASSO- with 4 copies of the allele, (Fisher’s PSLD-test; p = 0.026, CIATED VNTR AND CELLULAR MAO A ACTIVITY IN p = 0.018, p = 0.010, respectively). HUMAN MALE SKIN FIBROBLASTS. Denney RM, Koch The present results suggest that the structure of the HG and Craig IW.. MAOA promoter might be one factor underlying the SGDP Research Centre, Institute of Psychiatry, De expression of certain personality characteristics in Cauca- Crespigny Park, Denmark Hill, London, UK and Depart- sian males, possibly by influencing transcription of the ment of HBC and G, University of Texas Medical Branch, MAOA gene, and thereby the amount of active enzyme Galveston, TX. AVNTR located 1.2 kb upstream from molecules. MAO A exon 1 (uVNTR) is reportedly associated with panic disorder and compulsive eating disorder in females, and antisocial behavior in male alcoholics. Two labora- 234. ASSOCIATION ANALYSIS BETWEEN A FUNC- tories have shown that the three repeat allele at this locus TIONAL VNTR POLYMORPHISM IN THE PROMOTER confers lower promoter activity than the four repeat allele REGION OF MONOAMINE OXIDASE-A GENE AND when tested by transient expression in cultured cell lines. MOOD DISORDERS. Ishida S1, Kunugi H1, Kato T2, Tats- We report that uVNTR genotype has a quantitatively simi- umi M3, Sakai T3, Hattori M1, Hirose T1, Nanko S1. lar effect on cellular MAO A activity in cultured human 1Department of Psychiatry, Teikyo University School of skin fibroblasts. MAO A specific activity was significantly Medicine, Tokyo, Japan 2Department of Neuropsychiatry, lower in cultures with three repeats than that in cultures Faculty of Medicine, University of Tokyo, Tokyo, Japan with four (1.6 ± 1.1 and 13 ± 12 nmol/hr/mg, respectively; 3Department of Psychiatry, Showa University School of P = 0.032). Immunofluorescence microscopy and flow Medicine, Tokyo, Japan. cytometry showed that MAO A expression was confined Sabol and colleagues (Hum Genet 103: 273–9, 1998) to a cell sub population varying in size from 0.5–85% of identified a common polymorphism of a variable number cells in different cultures. This variability was not associa- tandem repeat (VNTR) in the promoter region of the ted with genotype, and generated additional variation in monoami oxidase-A (MAOA) gene, which was shown to activity within genotypes and overlap between genotypes. be associated with MAOA transcriptional activity. We Mean specific activity in MAO A+ cells (whole culture examined whether this functional polymorphism is asso- specific activity divided by the proportion of immunopos- ciated with the risk of developing mood disorders in a itive cells) again was lower for cells with three repeats Japanese sample of 161 patients with bipolar disorder, 98 than for cells with four (7.2 ± 3.1 and 23.9 ± with unipolar depression, and 258 controls. For the par- 9.5 nmol/hr/mg protein, respectively; P = 0.0013), with ticipation in the study, written informed consent was much less variation within and no overlap in activity obtained from each subject. We found a novel allele which between genotypes. Finding low fibroblast MAO A was not described by Sabol et al (1998), although its fre- activity in cells with three repeats is consistent with tran- quency was rare. Excluding this allele from the analyses, sient expression data, and suggests that uVNTR genotype there was no significant genotypic or allelic association, may be a major source of individual differences in sero- suggesting that the functional VNTR polymorphism in the tonin and norepinephrine oxidizing capacity. MAOA gene is unlikely to play a major role in the patho- genesis of bipolar disorder or unipolar depression in the Japanese sample. In addition, we found no significant 233. MAOA PROMOTER GENOTYPE IS RELATED TO association between the polymorphism and a history of PERSONALITY TRAITS.
Load more

Recommended publications
  • Neurotransmitter Resource Guide
    NEUROTRANSMITTER RESOURCE GUIDE Science + Insight doctorsdata.com Doctor’s Data, Inc. Neurotransmitter RESOURCE GUIDE Table of Contents Sample Report Sample Report ........................................................................................................................................................................... 1 Analyte Considerations Phenylethylamine (B-phenylethylamine or PEA) ................................................................................................. 1 Tyrosine .......................................................................................................................................................................................... 3 Tyramine ........................................................................................................................................................................................4 Dopamine .....................................................................................................................................................................................6 3, 4-Dihydroxyphenylacetic Acid (DOPAC) ............................................................................................................... 7 3-Methoxytyramine (3-MT) ............................................................................................................................................... 9 Norepinephrine ........................................................................................................................................................................
    [Show full text]
  • Review Paper Monoamine Oxidase Inhibitors: a Review Concerning Dietary Tyramine and Drug Interactions
    PsychoTropical Commentaries (2016) 1:1 – 90 © Fernwell Publications Review Paper Monoamine Oxidase Inhibitors: a Review Concerning Dietary Tyramine and Drug Interactions PK Gillman PsychoTropical Research, Bucasia, Queensland, Australia Abstract This comprehensive monograph surveys original data on the subject of both dietary tyramine and drug interactions relevant to Monoamine Oxidase Inhibitors (MAOIs), about which there is much outdated, incorrect and incomplete information in the medical literature and elsewhere. Fewer foods than previously supposed have problematically high tyramine levels because international food hygiene regulations have improved both production and handling. Cheese is the only food that has, in the past, been associated with documented fatalities from hypertension, and now almost all ‘supermarket’ cheeses are perfectly safe in healthy-sized portions. The variability of sensitivity to tyramine between individuals, and the sometimes unpredictable amount of tyramine content in foods, means a little knowledge and care are still advised. The interactions between MAOIs and other drugs are now well understood, are quite straightforward, and are briefly summarized here (by a recognised expert). MAOIs have no apparently clinically relevant pharmaco-kinetic interactions, and the only significant pharmaco-dynamic interaction, other than the ‘cheese reaction’ (caused by indirect sympatho-mimetic activity [ISA], is serotonin toxicity ST (aka serotonin syndrome) which is now well defined and straightforward to avoid by not co-administering any drug with serotonin re-uptake inhibitor (SRI) potency. There are no therapeutically used drugs, other than SRIs, that are capable of inducing serious ST with MAOIs. Anaesthesia is not contra- indicated if a patient is taking MAOIs. Most of the previously held concerns about MAOIs turn out to be mythical: they are either incorrect, or over-rated in importance, or stem from apprehensions born out of insufficient knowledge.
    [Show full text]
  • S41598-021-90243-1.Pdf
    www.nature.com/scientificreports OPEN Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS‑COV‑2 infection Miroslava Cuperlovic‑Culf1,2*, Emma L. Cunningham3, Hossen Teimoorinia4, Anuradha Surendra1, Xiaobei Pan5, Stefany A. L. Bennett2,6, Mijin Jung5, Bernadette McGuiness3, Anthony Peter Passmore3, David Beverland7 & Brian D. Green5* Delirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS‑CoV‑2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium‑ susceptibility in the postoperative setting using metabolomic profling of cerebrospinal fuid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found signifcant concentration diferences in several amino acids, acylcarnitines and polyamines linking delirium‑prone patients to known factors in Alzheimer’s disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein–protein docking analysis showed that there potentially is strong binding of SARS‑CoV‑2 spike protein to MAOB. The possibility that SARS‑CoV‑2 infuences MAOB activity leading to the observed neurological and platelet‑based complications of SARS‑CoV‑2 infection requires further investigation. COVID-19 is an ongoing major global health emergency caused by severe acute respiratory syndrome coro- navirus SARS-CoV-2. Patients admitted to hospital with COVID-19 show a range of features including fever, anosmia, acute respiratory failure, kidney failure and gastrointestinal issues and the death rate of infected patients is estimated at 2.2%1.
    [Show full text]
  • The Effects of Phenelzine and Other Monoamine Oxidase Inhibitor
    British Journal of Phammcology (1995) 114. 837-845 B 1995 Stockton Press All rights reserved 0007-1188/95 $9.00 The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver 12 imidazoline-preferring receptors Regina Alemany, Gabriel Olmos & 'Jesu's A. Garcia-Sevilla Laboratory of Neuropharmacology, Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, E-07071 Palma de Mallorca, Spain 1 The binding of [3H]-idazoxan in the presence of 106 M (-)-adrenaline was used to quantitate 12 imidazoline-preferring receptors in the rat brain and liver after chronic treatment with various irre- versible and reversible monoamine oxidase (MAO) inhibitors. 2 Chronic treatment (7-14 days) with the irreversible MAO inhibitors, phenelzine (1-20 mg kg-', i.p.), isocarboxazid (10 mg kg-', i.p.), clorgyline (3 mg kg-', i.p.) and tranylcypromine (10mg kg-', i.p.) markedly decreased (21-71%) the density of 12 imidazoline-preferring receptors in the rat brain and liver. In contrast, chronic treatment (7 days) with the reversible MAO-A inhibitors, moclobemide (1 and 10 mg kg-', i.p.) or chlordimeform (10 mg kg-', i.p.) or with the reversible MAO-B inhibitor Ro 16-6491 (1 and 10 mg kg-', i.p.) did not alter the density of 12 imidazoline-preferring receptors in the rat brain and liver; except for the higher dose of Ro 16-6491 which only decreased the density of these putative receptors in the liver (38%). 3 In vitro, phenelzine, clorgyline, 3-phenylpropargylamine, tranylcypromine and chlordimeform dis- placed the binding of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors from two distinct binding sites.
    [Show full text]
  • Monoamine Oxidase a Gene Promoter Variation and Rearing Experience Influences Aggressive Behavior in Rhesus Monkeys Timothy K
    Monoamine Oxidase A Gene Promoter Variation and Rearing Experience Influences Aggressive Behavior in Rhesus Monkeys Timothy K. Newman, Yana V. Syagailo, Christina S. Barr, Jens R. Wendland, Maribeth Champoux, Markus Graessle, Stephen J. Suomi, J. Dee Higley, and Klaus-Peter Lesch Background: Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences. We tested the hypothesis that a repeat polymorphism in the rhesus macaque MAOA gene promoter region influences aggressive behavior in male subjects. Methods: Forty-five unrelated male monkeys raised with or without their mothers were tested for competitive and social group aggression. Functional activity of the MAOA gene promoter polymorphism was determined and genotypes scored for assessing genetic and environmental influences on aggression. Results: Transcription of the MAOA gene in rhesus monkeys is modulated by an orthologous polymorphism (rhMAOA-LPR) in its upstream regulatory region. High- and low-activity alleles of the rhMAOA-LPR show a genotype ϫ environment interaction effect on aggressive behavior, such that mother-reared male monkeys with the low-activity-associated allele had higher aggression scores. Conclusions: These results suggest that the behavioral expression of allelic variation in MAOA activity is sensitive to social experiences early in development and that its functional outcome might depend on social context. Key Words: MAOA, promoter, VNTR, rearing, aggression, rhesus large family (Brunner et al 1993). Affected male subjects exhibit markedly disturbed monoamine metabolism and an absence of he interaction between genes and environment has long MAOA enzymatic activity in cultured fibroblasts.
    [Show full text]
  • Redox Biology 7 (2016) 21–29
    Redox Biology 7 (2016) 21–29 Contents lists available at ScienceDirect Redox Biology journal homepage: www.elsevier.com/locate/redox Research Paper The antimalarial drug primaquine targets Fe–S cluster proteins and yeast respiratory growth Anaïs Lalève a, Cindy Vallières b, Marie-Pierre Golinelli-Cohen c, Cécile Bouton c, Zehua Song a, Grzegorz Pawlik a,1, Sarah M. Tindall b, Simon V. Avery b, Jérôme Clain d, Brigitte Meunier a,n a Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris‐Sud, Université Paris‐Saclay, 91198 Gif‐sur‐Yvette cedex, France b School of Life Sciences, University Park, University of Nottingham, NG7 2RD, Nottingham, UK c Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France d UMR 216, Faculté de Pharmacie de Paris, Université Paris Descartes, and Institut de Recherche pour le Développement, 75006 Paris, France article info abstract Article history: Malaria is a major health burden in tropical and subtropical countries. The antimalarial drug primaquine Received 13 October 2015 is extremely useful for killing the transmissible gametocyte forms of Plasmodium falciparum and the Received in revised form hepatic quiescent forms of P. vivax. Yet its mechanism of action is still poorly understood. In this study, 22 October 2015 we used the yeast Saccharomyces cerevisiae model to help uncover the mode of action of primaquine. We Accepted 22 October 2015 found that the growth inhibitory effect of primaquine was restricted to cells that relied on respiratory function to proliferate and that deletion of SOD2 encoding the mitochondrial superoxide dismutase se- Keywords: verely increased its effect, which can be countered by the overexpression of AIM32 and MCR1 encoding Mitochondria mitochondrial enzymes involved in the response to oxidative stress.
    [Show full text]
  • Functional Role of Mitochondrial Reactive Oxygen Species in Physiology
    FUNCTIONAL ROLE OF MITOCHONDRIAL REACTIVE OXYGEN SPECIES IN PHYSIOLOGY Plamena R. Angelova and Andrey Y. Abramov Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London Corresponding authors: Dr Plamena R. Angelova and Prof Andrey Y. Abramov, Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square House, Queen Square, London, WC1N 3BG, United Kingdom. Emails: p. [email protected] or [email protected] ABSTRACT The major energy generator in the cell – mitochondria produce reactive oxygen species as a by-product of a number of enzymatic reactions and ATP production. Emerging evidence suggests that mitochondrial ROS regulate diverse physiological parameters and that dysregulated ROS signalling may contribute to a development of pathologies which leads to human diseases. ROS produced in mitochondrial enzymes are trigger for monoamine-induced calcium signal in astrocytes, playing important role in physiological and pathophysiological response to dopamine. Generation of ROS in mitochondria leads to peroxidation of lipids, which is considered to be one of the most important mechanisms of cell injury under condition of oxidative stress. However, it also can induce activation of mitochondrial and cellular phospholipases that can trigger variety of the signals – from activation of ion channels to stimulation of calcium signal. Mitochondria are shown to be the oxygen sensor in astrocytes, therefore inhibition of respiration by hypoxia induces ROS production which leads to lipid peroxidation, activation of phospholipase C and induction of IP3-mediated calcium signal. Propagation of astrocytic calcium signal stimulates breathing activity in response to hypoxia. Thus, ROS produced in mitochondrial enzymes or electron transport chain can be used as a trigger for signalling cascades in central nervous system and deregulation of this process leads to pathology.
    [Show full text]
  • Biological Application and Disease of Oxidoreductase Enzymes Mezgebu Legesse Habte and Etsegenet Assefa Beyene
    Chapter Biological Application and Disease of Oxidoreductase Enzymes Mezgebu Legesse Habte and Etsegenet Assefa Beyene Abstract In biochemistry, oxidoreductase is a large group of enzymes that are involved in redox reaction in living organisms and in the laboratory. Oxidoreductase enzymes catalyze reaction involving oxygen insertion, hydride transfer, proton extraction, and other essential steps. There are a number of metabolic pathways like glycolysis, Krebs cycle, electron transport chain and oxidative phosphorylation, drug transfor- mation and detoxification in liver, photosynthesis in chloroplast of plants, etc. that require the direct involvements of oxidoreductase enzymes. In addition, degrada- tion of old and unnecessary endogenous biomolecules is catalyzed by a family of oxidoreductase enzymes, e.g., xanthine oxidoreductase. Oxidoreductase enzymes use NAD, FAD, or NADP as a cofactor and their efficiency, specificity, good biode- gradability, and being studied well make it fit well for industrial applications. In the near future, oxidoreductase may be utilized as the best biocatalyst in pharmaceuti- cal, food processing, and other industries. Oxidoreductase play a significant role in the field of disease diagnosis, prognosis, and treatment. By analyzing the activities of enzymes and changes of certain substances in the body fluids, the number of disease conditions can be diagnosed. Disorders resulting from deficiency (quantita- tive and qualitative) and excess of oxidoreductase, which may contribute to the metabolic abnormalities and decreased normal performance of life, are becoming common. Keywords: biocatalyst, biological application, disease, metabolism, mutation, oxidoreductase 1. Introduction Oxidoreductases, which includes oxidase, oxygenase, peroxidase, dehydroge- nase, and others, are enzymes that catalyze redox reaction in living organisms and in the laboratory [1].
    [Show full text]
  • Bound Monoamine Oxidase: Ph and Temperature Dependences
    Inhibitory Effect of NaCI on Hog Kidney Mitochondrial Membrane- Bound Monoamine Oxidase: pH and Temperature Dependences Yoko Omura Department of Chemistry, Kanagawa Prefectural College of Nursing and Medical Technology, 50-1 Nakao-Cho, Yokohama 241, Japan Received April 12, 1995 Accepted September 5, 1995 ABSTRACT-For a further understanding of the inhibitory effect of NaCI on hog kidney mitochondrial monoamine oxidase (MAO), the activity for benzylamine as substrate was assayed spectrophotometrically in the absence and presence of NaCI for mitochondrial outer membrane preparations as well as whole mitochondria. The effect of CaC12 was also examined for comparison. The inhibition by NaCI but not CaC12 was strongly pH dependent. The pH dependence of the inhibitory effect of NaCI in phosphate buffer was parallel to the pH dependence of the MAO activity itself. The point at which the slope of the Arrhenius plot in the absence of NaCl decreases with increasing temperature was to be 32.31C at pH 7.0 and 30.41C at pH 7.5 in phosphate buffer, while the Arrhenius plot in the presence of NaCI exhibited discontinuities without change in the slope in small temperature ranges, 39.21C -40.01C and 33.0'C -34.21C. It was esti- mated that the inhibitory effect of NaCl was due to a pH and temperature sensitive cooperative state change involving MAO protein and boundary lipids, while the effect of CaC12 could be induced by specific Ca 21 binding to acidic phospholipids. Keywords: Hog kidney monoamine oxidase, Whole mitochondria, Mitochondrial outer membrane, Inhibitory effect of NaCl, Arrhenius plot Monoamine oxidase (MAO, EC 1.
    [Show full text]
  • Genetic and Proteinic Linkage of MAO and COMT with Oral Potentially Malignant Disorders and Cancers of the Oral Cavity and Pharynx
    cancers Article Genetic and Proteinic Linkage of MAO and COMT with Oral Potentially Malignant Disorders and Cancers of the Oral Cavity and Pharynx Ping-Ho Chen 1,2,3,4,5,6 , Yen-Yun Wang 1,4,5, Ting-Hsun Lan 1,7 , Leong-Perng Chan 6,8,9 and Shyng-Shiou Yuan 4,5,10,11,12,13,* 1 School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; [email protected] (P.-H.C.); [email protected] (Y.-Y.W.); [email protected] (T.-H.L.) 2 Institute of Biomedical Sciences, National Sun Yat-Sen University, No. 70 Lienhai Road, Kaohsiung 804201, Taiwan 3 Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan 4 Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807378, Taiwan 5 Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan 6 Cohort Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; [email protected] 7 Division of Prosthodontics, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan 8 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan 9 Department of Otorhinolaryngology-Head and Neck Surgery, Kaohsiung Municipal Ta-Tung Hospital and Citation: Chen, P.-H.; Wang, Y.-Y.; Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan Lan, T.-H.; Chan, L.-P.; Yuan, S.-S. 10 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan Genetic and Proteinic Linkage of 11 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, MAO and COMT with Oral Kaohsiung 807378, Taiwan 12 Potentially Malignant Disorders and Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan 13 Cancers of the Oral Cavity and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Pharynx.
    [Show full text]
  • 13 Reasons Why the Brain Is Susceptible to Oxidative Stress T ⁎ James Nathan Cobleya, , Maria Luisa Fiorelloa, Damian Miles Baileyb
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of South Wales Research Explorer Redox Biology 15 (2018) 490–503 Contents lists available at ScienceDirect Redox Biology journal homepage: www.elsevier.com/locate/redox Review article 13 reasons why the brain is susceptible to oxidative stress T ⁎ James Nathan Cobleya, , Maria Luisa Fiorelloa, Damian Miles Baileyb a Free Radical Laboratory, Departments of Diabetes and Cardiovascular Sciences, Centre for Health Sciences, University of the Highlands and Islands, Inverness IV2 3HJ, UK b Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, CF37 4AT, UK ARTICLE INFO ABSTRACT Keywords: The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal ac- Mitochondria tivity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia Brain is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neu- Redox signalling rodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to Oxidative stress oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O Neurodegeneration 2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity) through redox signalling (i.e. positive functionality). Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e.
    [Show full text]
  • The Relationship of Alcohol Dependence to Monoamine Oxidase A
    The Relationship of Alcohol Dependence to Monoamine Oxidase A by Brittany Matthews A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Pharmacology and Toxicology University of Toronto © Copyright by Brittany Matthews 2015 The Relationship of Alcohol Dependence to Monoamine Oxidase A Brittany Matthews Doctor of Philosophy Department of Pharmacology and Toxicology University of Toronto 2015 Abstract Background: Alcohol dependence (AD) is a substance abuse disorder characterized by compulsive alcohol seeking and intake, combined with a negative emotional state during withdrawal. AD is also associated with markers of apoptosis and/or oxidative stress across multiple organs. Monoamine oxidase A (MAO-A) is an important enzyme that participates in the cellular response to oxidative stress, and is elevated during major depressive episodes, somewhat more robustly in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). It is unknown whether MAO-A levels are abnormal in AD. The current studies examine whether: i) MAO-A level is elevated in the PFC and ACC in AD in humans. ii) Chronic harman exposure, a MAO-A inhibitor found in alcoholic beverages, upregulates MAO-A in the PFC and ACC of rodents. iii) Chronic alcohol exposure upregulates MAO-A in the PFC and ACC of rodents. Methods: i) Sixteen participants with AD underwent [ 11 C]-harmine positron emission tomography to determine MAO-A distribution volume (VT), an index of MAO-A level. ii ii) Rats were treated with harman for 21 days (0, 2, 5, 15 mg/kg/day) via osmotic minipump. MAO-A protein and activity levels, measured with Western blot and a spectrophotometric assay respectively, were assessed immediately and after 8-hour withdrawal.
    [Show full text]