Distribution of catechol-O-methyltransferase (COMT) proteins and enzymatic activities in wild-type and soluble COMT deficient mice
Distribution of catechol-O-methyltransferase (COMT) proteins and enzymatic activities in wild-type and soluble COMT deficient mice
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DOI：
10.1111/j.1471-4159.2010.06723.x
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发表时间：
2010-06-01
影响因子：
4.7
通讯作者：
Mannisto, Pekka T.
中科院分区：
文献类型：
--
作者：
Myohanen, Timo T.;Schendzielorz, Nadia;Mannisto, Pekka T.
P>；邻苯二酚-O-甲基转移酶(COMT)有可溶性(S-COMT)和膜结合型(MB-COMT)两种亚型。用一种特异性的COMT抗体进行免疫组织化学和共聚焦共定位研究，以探讨COMT在正常小鼠中的普遍分布，特别是MB-COMT在S-COMT缺陷小鼠系中的分布。在外周组织中，肝脏和肾脏中的COMT蛋白和活性水平较高，而在脑中，COMT的表达和活性较低。MB-COMT在所有组织中广泛分布，总体上与S-COMT的分布相似。MB-COMT表现出对脑组织的一些偏好，特别是在海马区。在大脑皮层和下丘脑也有明显的MB-COMT相关酶活性。MB-COMT和S-COMT一样，被发现是一种细胞内酶，但它与大脑中的质膜无关。这两种形式的COMT都广泛存在于小胶质细胞和肠道巨噬细胞中，但也存在于星形胶质细胞中。COMT也存在于锥体细胞、小脑浦肯野细胞、颗粒细胞和纹状体棘细胞等神经元中，但不存在于主要的长投射神经元中。最后，似乎在S-COMT缺陷小鼠中看不到核COMT。
P>Catechol-O-methyltranferase (COMT) has both soluble (S-COMT) and membrane-bound (MB-COMT) isoforms. A specific COMT antibody was used in immunohistochemical and confocal co-localization studies to explore the distribution of COMT in general in normal mice and MB-COMT in particular, in an S-COMT deficient mouse line. In the peripheral tissues, high COMT protein and activity levels were observed in liver and kidney, whereas in the brain, COMT expression and activity were much lower. MB-COMT was widely distributed throughout all tissues, and overall, the MB-COMT distribution mimicked the distribution of S-COMT. MB-COMT displayed some preference for brain tissue, notably in the hippocampus. MB-COMT related enzymatic activity was also pronounced in the cerebral cortical areas and hypothalamus. MB-COMT, like S-COMT, was found to be an intracellular enzyme but it was not associated with plasma membranes in the brain. Both COMT forms were abundantly found in microglial cells and intestinal macrophages, but also in astroglial cells. COMT was also present in some neuronal cells, like pyramidal neurons, cerebellar Purkinje and granular cells and striatal spiny neurons, but not in major long projection neurons. Finally, it seemed that nuclear COMT is not visible in S-COMT deficient mice.