Denney R M
Graduate School of Biomedical Sciences, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, USA.
J Neural Transm Suppl. 1998;52:17-27. doi: 10.1007/978-3-7091-6499-0_3.
Total deficiency of monoamine oxidase A (MAO-A) in affected males of a single, human kindred appears to be associated with mild mental retardation and significant behavioral anomalies. Though total MAO-A deficiency appears to be rare, the extent and significance of individual variation in monoamine oxidase A activity in human populations is unclear. Since MAO-A activity is undetectable in blood cells, most systematic surveys of individual variation MAO-A activity have compared enzyme activity in human fibroblasts cultured from skin biopsies. Surprisingly, MAO-A activity in skin fibroblast cultures from unrelated donors ranges over 100-fold. It has been suggested that this extreme variation in fibroblast MAO-A activity between donors reflects individual, genetic variation in the regulation of MAO-A in fibroblasts. I have found from studies with immunofluorescence microscopy and flow cytometry that the proportion of MAO-A+ cells in fibroblast cultures is (a) highly variable between cultures, (b) a reproducible characteristic of each culture and (c) the primary factor responsible for variation in MAO-A specific activity in whole cell, skin fibroblast homogenates. It has been shown previously that MAO-A activity of a skin fibroblast culture is relatively constant with continued passage prior to cellular senescence. Therefore, these new data raise the possibility that MAO-A expression is confined to a functionally distinct subset of human skin fibroblasts.
在一个人类家系中，受影响男性的单胺氧化酶A（MAO-A）完全缺乏似乎与轻度智力迟钝和明显的行为异常有关。虽然MAO-A完全缺乏似乎很罕见，但人群中单胺氧化酶A活性的个体差异程度和意义尚不清楚。由于血细胞中检测不到MAO-A活性，大多数关于MAO-A活性个体差异的系统调查都比较了从皮肤活检培养的人成纤维细胞中的酶活性。令人惊讶的是，来自无关供体的皮肤成纤维细胞培养物中的MAO-A活性范围超过100倍。有人认为，供体之间成纤维细胞MAO-A活性的这种极端差异反映了成纤维细胞中MAO-A调节的个体遗传差异。我通过免疫荧光显微镜和流式细胞术研究发现，成纤维细胞培养物中MAO-A+细胞的比例（a）在不同培养物之间高度可变，（b）是每种培养物的可重复特征，（c）是全细胞皮肤成纤维细胞匀浆中MAO-A比活性变化的主要因素。先前已经表明，皮肤成纤维细胞培养物的MAO-A活性在细胞衰老之前随着传代而相对恒定。因此，这些新数据增加了MAO-A表达局限于人类皮肤成纤维细胞功能上不同亚群的可能性。
