Saneto R P, Low K G, Melner M H, de Vellis J
Department of Neuroscience, Oregon Regional Primate Research Center, Beaverton.
J Neurosci Res. 1988 Oct-Dec;21(2-4):210-9. doi: 10.1002/jnr.490210213.
The expression of myelin basic protein by the oligodendrocyte is an integral event in the maturation of central nervous system function. Although much is known concerning the various myelin basic protein species, their temporal expression, and processing of RNA transcripts, little is known about the epigenetic factors responsible for the regulation of myelin basic protein (MBP) expression. In this study, we present evidence that insulin/insulin-like growth factor-I can increase the levels of MBP protein in isolated oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium (ODM). Insulin was found to increase MBP protein in a dose-responsive manner, reaching a maximal level at 72 hr of exposure. Both insulin-like growth factor-I (IGF-I) and insulin were demonstrated to have no effect on MBP RNA levels. These data indicate that insulin/IGF-I increased MBP protein levels at a level distal to transcription The dose response of insulin action suggests that it may have a MBP regulatory function, distinct from IGF-I. When added individually, the other supplements of ODM, transferrin (500 ng/ml), and basic fibroblast growth factor (5 ng/ml) had no effect on MBP expression. However, when all three components were combined, a synergistic effect resulting in increased MBP protein and total RNA levels was found. The phorbol ester 12-O-tetradecanoyl phorbol acetate was found to reduce intracellular MBP RNA levels. The cAMP analogue/dibutyryl cAMP had contrasting effects on MBP RNA levels; no effect occurred in cultures grown in fetal calf serum, but a reduction in RNA levels was found in cultures grown in ODM. These data suggest that only a select range of extrinsic factors may be involved in MBP regulation, and depending on the environmental milieu, epigenetic agents may modulate gene activity differently.
少突胶质细胞表达髓鞘碱性蛋白是中枢神经系统功能成熟过程中的一个重要事件。尽管我们对各种髓鞘碱性蛋白种类、它们的时序表达以及RNA转录本的加工过程已经有了很多了解，但对于负责调节髓鞘碱性蛋白（MBP）表达的表观遗传因素却知之甚少。在本研究中，我们提供证据表明胰岛素/胰岛素样生长因子-I能够增加在无血清、化学成分确定的培养基（ODM）中培养的分离少突胶质前体细胞中MBP蛋白的水平。发现胰岛素以剂量反应方式增加MBP蛋白水平，在暴露72小时时达到最高水平。胰岛素样生长因子-I（IGF-I）和胰岛素均被证明对MBP RNA水平没有影响。这些数据表明胰岛素/IGF-I在转录远端水平增加了MBP蛋白水平。胰岛素作用的剂量反应表明它可能具有与IGF-I不同的MBP调节功能。当单独添加时，ODM的其他补充成分转铁蛋白（500 ng/ml）和碱性成纤维细胞生长因子（5 ng/ml）对MBP表达没有影响。然而，当这三种成分组合在一起时，发现有协同作用，导致MBP蛋白和总RNA水平增加。佛波酯12-O-十四酰佛波醇-13-乙酸酯被发现可降低细胞内MBP RNA水平。cAMP类似物/二丁酰cAMP对MBP RNA水平有相反的影响；在胎牛血清中培养的细胞中没有影响，但在ODM中培养的细胞中发现RNA水平降低。这些数据表明只有特定范围的外在因素可能参与MBP调节，并且根据环境背景，表观遗传因子可能以不同方式调节基因活性。
