Chen Kevin
Department of Molecular Pharmacology and Toxicology, Pharmaceutical Science Center, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Neurotoxicology. 2004 Jan;25(1-2):31-6. doi: 10.1016/S0161-813X(03)00113-X.
Monoamine oxidase (MAO) A and B play important roles in the metabolism of catecholamines and xenobiotics in the central nervous system and peripheral tissues. The ubiquitous presence of low level of MAO in all cells suggests essential functional for house keeping. Higher level of expression of MAO A and B also were observed in tissue and cell specific manner. The core promoter of human MAO A and B promoters have been characterized. Sp1 binding motifs were present in both promoters which constituted the major binding sites for Sp1 and Sp1-like family transcription factor binding, and other interaction proteins like Egr-1 in MAO B promoter. The presence of repeat units within the 2 kb human MAO A promoter which is associated with promoter activity and enzymatic activity in human fibroblast culture provided a tool to study human population with abnormal behaviors related to serotonin and other neurotransmitters. Conflicting results were reported from these studies due to the lack of basic understanding of MAO A promoter and the factors such as glucocorticoid which influences MAO A activity. Hopefully the enthusiasm will lead to more reliable tools to identify the major factor which caused the large difference in MAO A activity among human population. The overlapping Sp1/Egr-1/Sp1 binding site within MAO B promoter has been identified as the responsible element for PMA response. MAO B expression is selectively induced by the activation of protein kinase C and MAPK signal pathway.
单胺氧化酶(MAO)A和B在中枢神经系统和外周组织中儿茶酚胺及外源性物质的代谢过程中发挥着重要作用。所有细胞中普遍存在低水平的MAO,这表明其在维持细胞基本功能方面具有重要作用。MAO A和B在组织和细胞中的表达也呈现出特异性的高水平。人类MAO A和B启动子的核心区域已得到表征。两种启动子中均存在Sp1结合基序,它们构成了Sp1及Sp1样家族转录因子的主要结合位点,MAO B启动子中还存在其他相互作用蛋白,如Egr-1。人类MAO A启动子2 kb范围内的重复单元与人类成纤维细胞培养中的启动子活性及酶活性相关,这为研究与血清素及其他神经递质相关的异常行为人群提供了一种工具。由于对MAO A启动子以及影响MAO A活性的因素(如糖皮质激素)缺乏基本了解,这些研究报告的结果相互矛盾。希望这种热情能够带来更可靠的工具,以确定导致人群中MAO A活性存在巨大差异的主要因素。MAO B启动子内重叠的Sp1/Egr-1/Sp1结合位点已被确定为对佛波酯(PMA)反应的负责元件。MAO B的表达可通过蛋白激酶C和丝裂原活化蛋白激酶(MAPK)信号通路的激活而被选择性诱导。