Our understanding of muscle glycosylation to date has derived from studies in mouse models and a limited number of human lectin histochemistry studies. As various therapeutic approaches aimed at treating patients with muscular dystrophies are being translated from rodent models to human, it is critical to better understand human muscle glycosylation and relevant disease-specific differences between healthy and dystrophic muscle. Here, we report the first quantitative characterization of human muscle glycosylation, and identify differentiation- and disease-specific differences in human muscle glycosylation. Utilizing a panel of 13 lectins with varying glycan specificities, we surveyed lectin binding to primary and immortalized myoblasts and myotubes from healthy and dystrophic sources. Following differentiation of primary and immortalized healthy human muscle cells, we observed increased binding of Narcissus pseudonarcissus agglutinin (NPA), PNA, MAA-II and WFA to myotubes compared to myoblasts. Following differentiation of immortalized healthy and dystrophic human muscle cells, we observed disease-specific differences in binding of NPA, Jac and Tricosanthes japonica agglutinin-I (TJA-I) to differentiated myotubes. We also observed differentiation- and disease-specific differences in binding of NPA, Jac, PNA, TJA-I and WFA to glycoprotein receptors in muscle cells. Additionally, Jac, PNA and WFA precipitated functionally glycosylated α-DG, that bound laminin, while NPA and TJA-I did not. Lectin histochemistry of healthy and dystrophic human muscle sections identified disease-specific differences in binding of O-glycan and sialic acid-specific lectins between healthy and dystrophic muscle. These results indicate that specific and discrete changes in glycosylation occur following differentiation, and identify specific lectins as potential biomarkers sensitive to changes in healthy human muscle glycosylation.

中文翻译：

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凝集素结合是健康人骨骼肌糖表型的特征，并鉴定营养不良性肌肉疾病的特异性变化

迄今为止，我们对肌肉糖基化的了解源自对小鼠模型的研究和数量有限的人类凝集素组织化学研究。随着旨在治疗患有肌营养不良患者的各种治疗方法已从啮齿动物模型转化为人类，至关重要的是更好地了解人类肌肉糖基化以及健康与营养不良肌肉之间相关的疾病特异性差异。在这里，我们报告人类肌肉糖基化的第一个定量表征，并确定人类肌肉糖基化的分化和疾病特异性差异。利用一组具有不同聚糖特异性的13种凝集素，我们调查了凝集素与原发性和永生化成肌细胞以及来自健康和营养不良来源的肌管的结合。与成肌细胞相比，成肌管的水仙假水仙凝集素（NPA），PNA，MAA-II和WFA。永生化的健康和营养不良的人类肌肉细胞分化后，我们观察到NPA，Jac和Tricosanthes japonica凝集素I（TJA-1）与分化的肌管结合的疾病特异性差异。我们还观察到NPA，Jac，PNA，TJA-1和WFA与肌细胞糖蛋白受体结合的分化和疾病特异性差异。此外，Jac，PNA和WFA会沉淀功能性糖基化的α-DG，与层粘连蛋白结合，而NPA和TJA-1没有。健康和营养不良的人类肌肉切片的凝集素组织化学鉴定了O结合的疾病特异性差异糖和唾液酸特异性凝集素介于健康和营养不良的肌肉之间。这些结果表明，糖基化的特异性和离散变化是在分化后发生的，并将特定的凝集素确定为对健康人肌肉糖基化变化敏感的潜在生物标记。