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TWO TYPES OF MONOAMINE OXIDASE

两种类型的单胺氧化酶

基本信息

批准号：
7209026
负责人：
Jean Chen Shih
金额：
$ 49.67万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 2008-12-28
项目状态：
已结题

项目摘要

DESCRIPTION: The objectives of this project are to understand the regulation and the in-vivo function of monoamine oxidase (MAO) A and B, which are isoenzymes important for the degradation of monoamine neurotransmitters and biogenic amines. Abnormal levels of MAO activity have been associated with a number of mental disorders. A better understanding of these isoenzymes will allow for the development of more effective treatments for mental disorders. The specific aims are outlined below: To study the function of both MAO A and B in neurotransmitter metabolism and behavior using double knock-out (KO) mice MAO A and B (A/B) double KO mice will be generated by inactivating the MAO A gene of MAO KO mice via homologous recombination. PCR, Southern blot analysis, MAO catalytic activity and Western blot analysis will be used to ensure that both MAO A and B are deficient in these mice. Brain levels (whole brain and regions) of serotonin, norepinephrine and dopamine (MAO A substrates) and their metabolites will be determined in MAO A/B double KO and wild type mice by high pressure liquid chromatography (HPLC). Brain levels of the neuromodulator B-phenylethylamine (MAO B substrate) will be determined by Gas Chromatography/Mass Spectrometry (GC-MS). These levels will be correlated with MAO A and B catalytic activity. Aggressive behavior will be analyzed in male MAO A/B double KO mice and correlated with brain neurotransmitter levels. II. To investigate the role of factors F, M and Sp1 in the regulation of MAO B gene expression. The essential DNA bases required for factors F and M binding will be determined by site-directed mutagenesis and the role of each factor in MAO B gene expression will be identified by gel retardation and promoter activity assays. Using UV crosslinking experiments we will determine if the factors comprise of a single or multiple polypeptides. Full-length cDNAs encoding factors F and M will be cloned and their functional validity will be determined by gel retardation assays with expressed proteins. The cDNA encoding factor F, M and Sp1 will be transfected and the effect of expressed factors on MAO B expression in vivo will be studied by determination of promoter activity, MAO B mRNA levels, protein levels and catalytic activity. These studies are important for both basic neuropharmacology and clinical research.

描述：这个项目的目标是了解

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

雌激素相关受体刺激的单胺氧化酶 B 启动子活性被雌激素受体下调。

DOI：
10.1210/me.2005-0252
发表时间：
2006
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
0
作者：
Zhang,Zhiping;Chen,Kevin;Shih,JeanC;Teng,ChristinaT
通讯作者：
Teng,ChristinaT

A novel role for glyceraldehyde-3-phosphate dehydrogenase and monoamine oxidase B cascade in ethanol-induced cellular damage.

DOI：
10.1016/j.biopsych.2009.10.032
发表时间：
2010-05-01
期刊：
BIOLOGICAL PSYCHIATRY
影响因子：
10.6
作者：
Ou, Xiao-Ming;Stockmeier, Craig A.;Meltzer, Herbert Y.;Overholser, James C.;Jurjus, George J.;Dieter, Lesa;Chen, Kevin;Lu, Deyin;Johnson, Chandra;Youdim, Moussa B. H.;Austin, Mark C.;Luo, Jia;Sawa, Akira;May, Warren;Shih, Jean C.
通讯作者：
Shih, Jean C.

Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload.

DOI：
10.1161/circresaha.109.198366
发表时间：
2010-01-08
期刊：
Circulation research
影响因子：
20.1
作者：
Kaludercic N;Takimoto E;Nagayama T;Feng N;Lai EW;Bedja D;Chen K;Gabrielson KL;Blakely RD;Shih JC;Pacak K;Kass DA;Di Lisa F;Paolocci N
通讯作者：
Paolocci N

Monoamine oxidases: from tissue homogenates to transgenic mice.

单胺氧化酶：从组织匀浆到转基因小鼠。