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首页> 外文期刊>The Open Pathology Journal >Tau Phosphorylation in Myotilinopathies and Desminopathies
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Tau Phosphorylation in Myotilinopathies and Desminopathies

机译：桃金娘病和脱蛋白病中的Tau磷酸化

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Tau expression and tau phosphorylation were examined in muscle biopsies of sporadic inclusion body myositis(sIBM), myotilinopathies and desminopathies compared with controls. A panel of anti-tau antibodies including 3Rtau,4Rtau, phospho-specific tau Thr181, Ser262, Ser396, Ser422 and antibody AT8 (recognizing phosphorylation sites Ser202and Thr205) and Alzh50 (conformation-dependent) showed diffuse staining in scattered fibers and peripheral or centralaggregates in sIBM, myotilinopathies and desminopathies when compared with controls. This was accompanied bysignificantly increased tau expresion on western blots immunostained with PHF1 antibody, which recognizes a band of120 kDa corresponding to big tau and several bands of lower molecular weight between 60 and 70 kDa, in sIBM andsome myotilinopatyhy cases. Increased tau accumulation is not accompanied by increased tau mRNA expression levelsbut by increased focal immunoreactivity in damaged fibers which is variable from one case to another. Increased tauimmunoreactivity is associated with increased focal expression of several kinases known to be involved in tauphosphorylation in vitro such as AKT-P, MAPK/ERK-P, GSK-3βSer9, GSK-3βTyr, and stress kinases SAPK/JNK-P andp38-P. These findings confirm previous observations in sIBM, but also demonstrate tau hyper-phosphorylation andabnormal deposition in damaged muscular fibers in myotilinopathies and desminopathies. Furthermore, the presentfindings suggest the involvement of varied kinases in the process of tau hyper-phosphorylation. GSK-3αβ appears to be acardinal kinase. In addition, activation of stress kinases SAPK/JNK and p38 link previously described oxidative stresswith tau phosphorylation in sIBM and myofibrillar myopathies. On the basis of these data, sIBM, myotilinopathies anddesminopathies can be considered secondary tauopathies affecting the skeletal muscle.
机译：与对照相比，在散发性包涵体肌炎（sIBM），肌铁蛋白病和脱蛋白病的肌肉活检中检查了tau表达和tau磷酸化。一组抗tau抗体，包括3Rtau，4Rtau，磷酸特异性tau Thr181，Ser262，Ser396，Ser422和抗体AT8（可识别磷酸化位点Ser202和Thr205）和Alzh50（视构象而定）在分散的纤维和周边或中央聚集物中均表现出弥漫性染色在sIBM中，与对照相比，肌原性肌病和脱髓鞘病。这伴随着用PHF1抗体免疫染色的Western印迹的tau表达显着增加，在sIBM和某些肌成纤维不全病例中，可识别对应于大tau的120 kDa条带和介于60至70 kDa的数条较低分子量的条带。 tau积累的增加并不伴随tau mRNA表达水平的提高，而是受损纤维中局部免疫反应性的提高，这在不同情况下是不同的。增强的tau免疫反应性与一些已知在体外参与tau磷酸化的激酶（例如AKT-P，MAPK / ERK-P，GSK-3βSer9，GSK-3βTyr）和应激激酶SAPK / JNK-P和p38-P的聚焦表达增加有关。这些发现证实了以前在sIBM中的观察结果，但也证明了tau过度磷酸化以及肌铁蛋白病和脱蛋白病的受损肌纤维中异常沉积。此外，本发明结果提示tau超磷酸化过程中涉及多种激酶。 GSK-3αβ似乎是主要的激酶。此外，应激激酶SAPK / JNK和p38的激活将先前描述的氧化应激与sIBM和肌原纤维肌病中的tau磷酸化联系起来。根据这些数据，可以将sIBM，肌铁蛋白病和脱皮病视为影响骨骼肌的继发性tauo病。

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