• Title/Summary/Keyword: Monoamine oxidase

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The Effects of Monoamine Oxidase A CA Repeat Polymorphism on Behavioral Trait and Clinical Characteristics in Korean Male Alcoholics (단가아민 산화제 A CA 반복 유전자 다형성이 한국 알코올의존 남자환자의 행동특성과 임상양상에 미치는 영향)

  • Lee, Jung-Sik;Yang, Byung-Hwan;Lee, Kyung-Mee;Kim, Hong-Kwan;Kim, Yong-In;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.7 no.1
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    • pp.64-73
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    • 2000
  • There are several candidate genes in genetic study of alcoholism. Among them, allelic associations have been reported between MAOA CA repeat polymorphism and alcohol dependence, recently. And also, several studies have been investigated genotype-phenotype relationships between MAOA CA repeat polymorphism and clinical manifestations. The authors tried to identify differences in allelic frequency of MAOA CA repeat polymorphism between alcohol dependence and controls, and in behavioral trait and clinical characteristics according to MAOA CA repeat polymorphism. We also tried to investigate genotype-phenotype relationships between MAOA CA repeat polymorphism and behavioral trait such as aggression. We examined 49 male patients with alcohol dependence(DSM-IV) who had been admitted in Yong-In Mental Hospital from June 1st 1998 to October 31th 1998. We performed semistructured interview for demographic and clinical characteristics. Self-report questionnaire for BDHI(Buss-Durkey Hostility Inventory) was given to all subject at least 4weeks later after admission. Using polymerase chain reaction and polyacrylamide gel electrophoresis, MAOA CA repeat polymorphism were observed in 52 male controls and 49 male patients with alcohol dependence. We devided alcoholic patients into two groups according to allelic length of MAOA CA repeat polymorphism ; alcoholics with short alleles(${\leq}$119bp, N=20) and alcoholics with long alleles(${\geq}$123bp, N=29). T-test, ${\chi}^2$-test and Fisher exact probability test were used for statistical analysis. There were no significant differences in frequency of each allele and short and long alleles of MAOA CA repeat polymorphism between alcoholics and controls. But there were significant differences in clinical symptoms and behavioral trait between alcoholics with short and long alleles. In clinical symptoms, alcoholics with long alleles used alcohol more frequently during one month before admission, had much more maximum amount of beer drinking and reported withdrawal seizure more frequently than with short alleles. In contrary, alcoholics with short alleles expressed depressed mood and guilty feeling more frequently and wanted complete abstinence as a treatment goal more frequently than with long alleles. In behavioral trait, alcoholics with long alleles had higher total aggression score and showed much more self-assertive attitude(subscale of expression of aggression) than with short alleles. Allelic length of MAOA CA repeat polymorphism was correlated with self-assertive attitude and accounted for 9% of the variance of self-assertive attitude. And also, predictable variables of allelic length of MAOA CA repeat polymorphism were drinking frequency and self-assertive attitude. Our findings suggest that MAOA CA repeat polymorphism may provide some behavior modifying role especially in self-assertive attitude and indirect symptom modifying role in Korean male alcoholics.

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Roles of Monoamine Neurotransmitters in Regulation of Hypothalamic PITUITITARY-ADRENAL AXIS(HPA) (III) - Role of 5-hydroxytryptamine in Controlling the Stress-Induced Elevation of Corticosterone in Rat - (시상하부-뇌하수체-부신계 조절에 대한 Monoamine 신경전달물질의 역할에 관한 연구(III)-뇌 5-hydroxytyptamine(Serotonin)이 Stress 시 Corticosteroid 변동에 미치는 영향)

  • Suh, Yoo-Hun;Lim, Jung-Kyoo;Park, Chan-Woong
    • The Korean Journal of Pharmacology
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    • v.19 no.2
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    • pp.45-55
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    • 1983
  • A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

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Effects of Pueraria thunbergiana Bentham Water Extracts on Hepatic Alcohol Metabolic Enzyme System In Rats (칡 열수추출물이 흰쥐의 알콜올 대사효소계에 미치는 영향)

  • 김명주;이정수;하오명;장주연;조수열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.1
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    • pp.92-97
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    • 2002
  • The effects of Pueraria flos (PF) and Pueraria radix (PR) water extract on the hepatic alcohol metabolic enzyme activities were examined in rats that were orally administered ethanol (25% v/v, 5g/kg body weight/day) for 5 weeks. The PF and PR water extract were supplemented in a diet, based on 1.2 g or 2.4 g of raw PF or PR/kg body weight/body. Alcohol administration without the PF or PR supplementation significantly decreased net weight gain, feed intake and feed efficiency ratio. However. both dose of the PF of PR supplementation resulted in significant enhancement of growth and suppression of increased relative weight of liver, brain and heart by alcohol administration. Activities of hepatic alcohol dehydrogenase and microsomal ethanol oxidizing system were higher in the alcohol treated group than in the normal group, while aldehyde dehydrogenase activity was significantly lowered in the alcohol treated group. The hepatic metabolic enzyme activities altered by alcohol administration were normalized by both doses of PF or PR supplement. Hepatic monoamine oxidase activity and hydrogen peroxide, which were significantly higher in the alcohol treated group than in the normal group, were also decreased by the supplementation with either PF or PR. These results indicate that low-or high-supplementation of either water extract PF or PR may alleviate ethanol-induced hepatotoxicity by altering alcohol metabolic enzyme activities.

Characterization of Three Extracellular β-Glucosidases Produced by a Fungal Isolate Aspergillus sp. YDJ14 and Their Hydrolyzing Activity for a Flavone Glycoside

  • Oh, Jong Min;Lee, Jae Pil;Baek, Seung Cheol;Jo, Yang Do;Kim, Hoon
    • Journal of Microbiology and Biotechnology
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    • v.28 no.5
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    • pp.757-764
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    • 2018
  • A cellulolytic fungus, YDJ14, was isolated from compost and identified as an Aspergillus sp. strain. Three extracellular ${\beta}$-glucosidases, BGL-A1, BGL-A2, and BGL-A3, were separated using ultrafiltration, ammonium sulfate fractionation, and High-Q chromatography. The molecular masses of the three enzymes were estimated to be 100, 45, and 40 kDa, respectively, by SDS-PAGE. The optimum pH and temperature of BGL-A3 were 5.0 and $50^{\circ}C$, respectively, whereas the optimum pH and temperature of BGL-A1 and BGL-A2 were identical (4.0 and $60^{\circ}C$, respectively). The half-life of BGL-A3 at $70^{\circ}C$ (2.8 min) was shorter than that of BGL-A1 and BGL-A2 (12.1 and 8.8 min, respectively). All three enzymes preferred p-nitrophenyl-${\beta}$-$\text\tiny{D}$-glucopyranoside (pNPG) and hardly hydrolyzed cellobiose, suggesting that these enzymes were aryl ${\beta}$-glucosidases. The $K_m$ of BGL-A3 (1.26 mM) for pNPG was much higher than that of BGL-A1 and BGL-A2 (0.25 and 0.27 mM, respectively). These results suggested that BGL-A1 and BGL-A2 were similar in their enzymatic properties, whereas BGL-A3 differed from the two enzymes. When tilianin (a flavone glycoside of acacetin) was reacted with the three enzymes, the inhibitory activity for monoamine oxidase, a target in the treatment of neurological disorders, was similar to that shown by acacetin. We conclude that these enzymes may be useful in the hydrolysis of flavone glycosides to improve their inhibitory activities.

Effect of Methionine Levels on Brain Lipid Peroxidation in Ethanol-treated Rats of Selenium Deficiency (메티오닌과 셀렌이 에탄올 중독된 흰쥐의 뇌지질과산화에 미치는 영향)

  • 조수열;이미경;박은미;장주연;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.1
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    • pp.109-115
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    • 1997
  • This study was designed to investigate the effects of methionine(Met) on the activities of brain lipid peroxidation related enzymes in ethanol administrated rats of selenium(Se) deficiency. Male Sprague-Dawley rats were fed Se deficiency diets containing one of the three levels of Met (0, 3, 9g/kg diet) and ethanol(2.5g/kg of body weight) was administrated as 25v/v% ethanol treated groups orally. The rats sacrificed after 5 and 10 weeks of feeding periods. Alcohol dehydrogenase activity was increased in ethanol treated groups and was higher Met normal group than Met deficiency and excessive groups at 5 and 10 weeks dieting. Aldehyde dehydrogenase activity was decreased in ethanol treated groups and significantly decreased in Met deficiency group. Monoamine oxidase activity in brain was increased in ethanol treated groups and was predominently increased in Met deficiency groups. Superoxide dismutase and glutathione peroxidase activities were decreased in ethanol treated groups and tended to increase in proportion to level of dietary methionine. Glutathione S-transferase and catalase activities and lipid peroxide content were increased by ethanol administration and were higher Met deficiency group than normal and excessive groups.

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Effects of the Deer Antler Extract on Scopolamine-induced Memory Impairment and Its Related Enzyme Activities (녹용 추출물이 치매 동물모델의 기억력 개선과 관련효소 활성에 미치는 효과)

  • Lee, Mi-Ra;Sun, Bai-Shen;Gu, Li-Juan;Wang, Chun-Yan;Fang, Zhe-Ming;Wang, Zhen;Mo, Eun-Kyoung;Ly, Sun-Young;Sung, Chang-Keun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.4
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    • pp.409-414
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    • 2009
  • The aim of this study was to investigate the ameliorating effects of deer antler extract on the learning and memory impairments induced by the administration of scopolamine (2 mg/kg, i.p.) in rats. Tacrine was used as a positive control agent for evaluating the cognition enhancing activity of deer antler extract in scopolamine-induced amnesia models. The results showed that the deer antler extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Morris water maze test. Although there was no statistical significance of brain ACh contents among the experimental groups, the brain ACh contents of the deer antler extract-treated group was slightly higher than that of the scopolamine-treated group. The inhibitory effect of deer antler extract on the acetylcholinesterase activity in the brain was significantly lower than that of scopolamine-treated group. The tacrine- and the deer antler-treated groups reduced the MAO-B activity compared to the scopolamine-treated group, but not significantly. These results suggest that the deer antler extract could be an effective agent for the prevention of the cognitive impairment induced by cholinergic dysfunction.

Inhibitory Effects of Amitriptyline, Sertraline and Chlorpromazine on the Thrombin-induced Aggregation of Platelets (Thrombin성 혈소판응집에 대한 Amitriptyline, Sertraline 및 Chlorpromazine의 억제작용)

  • Choi, Sang-Hyun;Lee, Young-Jae;Shin, Kyung-Ho;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.31 no.3
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    • pp.299-311
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    • 1995
  • Platelets resemble monoaminergic neurons in several respects, i.e. the uptake of 5-HT and its inhibition, the subcellular storage and release of 5-HT, and the metabolism of aromatic amines brought about by monoamine oxidase. And the 5-HT content of rabbit platelets is well known to be about 40 times higher than that of human platelets. Therefore, this study was carried out to investigate the influences of amitriptyline (AMT) and sertraline (SRT) on the aggregation, contents of signaling second messengers, and protein phosphorylations of rabbit platelets in response to thrombin, 0.25 unit/ml, comparing with those of chlorpromazine (CPZ). Thrombin-induced aggregation was inhibited by SRT $(IC50:4.37{\times}10^{-5}\;M)$, CPZ $(IC50:5.76{\times}10^{-5}\;M)$, and AMT $(IC50:1.15{\times}10^{-4}\;M)$, respectively, and the aggregation by A23187 $(1.0\;{\mu}M)$ or PMA (320 nM) was also inhibited by SRT, CPZ, and AMT. AMT, SRT, and CPZ had little affects on basal contents of platelet $TXB_2$ and $PGE_2$, but all of them inhibited the thrombin-induced increase of $TXB_2$. Thrombin did not change the platelet contents of cAMP and cGMP. CPZ, AMT, and SRT produced the slight decrease of basal cAMP content, and their effects were not affected by thrombin-treatment. But SRT and AMT moderately increased the basal cGMP content, and the cGMP content of thrombin-stimulated platelets was gradually increased by the pretreatment with SRT, AMT, and CPZ. Particularly, the SRT-dependent increase of the cGMP content was notable. Platelet $Ins(1,4,5)P_3$ content was rapidly increased up to a plateau within 10 sec after thrombin-stimulation, AMT, SRT, and CPZ increased the basal $Ins(1,4,5)P_3$ content, and the thrombin-dependent increase was enhanced by pretreatment with CPZ and AMT, but was blunted by SRT. Platelet $[Ca^{2+}]_i$, was rapidly increased up to a peak level within 20 sec after thrombin-stimulation. The increase of $[Ca^{2+}]_i$ was sisnificantly inhibited by AMT, SRT, and CPZ. Thrombin- or PMA-induced phosphorylations of platelet $41{\sim}43\;kDa$ and 20 kDa proteins were significantly inhibited by AMT, SRT, and CPZ. These results suggest that the antiplatelet activities of AMT and CPZ may be considerably attributed to the inhibition of protein kinase C activity, and the activity of SRT may be associated with the inhibitory effect on the thrombin-induced increase of $Ins(1,4,5)P_3$ and the increasing effect on the cGMP content of ptatelets. Therefore, it seems to be evident that AMT and SRT may produce their antidepressant activity, at least, partly through the inhibition of protein kinase C activity or the increase of resting $Ins(1,4,5)P_3$, content and in case of SRT, to a lesser extent, via the increase of cGMP in the brain.

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