Ksiezak-Reding Hanna, Farooq Muhammad, Yang Liang-sheng, Dickson Dennis W, LoPresti Patrizia
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Neurochem Res. 2003 Sep;28(9):1385-92. doi: 10.1023/a:1024952600774.
In tauopathies, overexpression of tau exon 10 is linked to degeneration and abnormal tau deposition in neurons and oligodendroglia (OLGs). To compare exon 10 expression in normal neurons and OLGs, adult bovine brain was examined for the expression of tau in gray matter and cultured OLGs isolated from white matter. Using exon-specific antibodies, we found that both types of tissues abundantly expressed exon 2 but isolated OLGs had a lower expression of exons 3 and 10 when compared to gray matter. Relative expression of exons 3 and 10 did not change significantly during the in vitro maturation of OLGs for 39 days. Using a panel of well-characterized antibodies against tau, we determined that isolated OLGs contained tau phosphorylated at the Tau-1, 12E8, and PHF-1 but not the AT8, AT100, AT180, and AT270 epitopes. Tau phosphorylation status diminished during in vitro maturation, suggesting that healthy OLG processes require regulated phosphorylation of tau at specific sites. We propose that the tau isoform profile and phosphorylation status contribute to the vulnerability of OLGs in degenerative diseases linked to overexpression of exon 10.
在tau蛋白病中，tau外显子10的过表达与神经元和少突胶质细胞（OLGs）的变性及异常tau沉积有关。为比较正常神经元和OLGs中外显子10的表达情况，对成年牛脑的灰质中tau的表达以及从白质中分离出的培养OLGs进行了检测。使用外显子特异性抗体，我们发现这两种组织均大量表达外显子2，但与灰质相比，分离出的OLGs中外显子3和10的表达较低。在OLGs体外成熟39天的过程中，外显子3和10的相对表达没有显著变化。使用一组针对tau的特征明确的抗体，我们确定分离出的OLGs含有在Tau-1、12E8和PHF-1位点磷酸化的tau，但不含有在AT8、AT100、AT180和AT270表位磷酸化的tau。在体外成熟过程中，tau的磷酸化状态降低，这表明健康的OLGs突起需要tau在特定位点进行调节性磷酸化。我们提出，tau异构体谱和磷酸化状态导致了在与外显子10过表达相关的退行性疾病中OLGs的易损性。
