Cieniewski-Bernard Caroline, Mounier Yvonne, Michalski Jean-Claude, Bastide Bruno
Unité Mixte de Recherche Centre National de la Recherche Scientifique 8576, Glycobiologie Structurale et Fonctionnelle, Institut Fédératif de Recherche 118, France.
J Appl Physiol (1985). 2006 May;100(5):1499-505. doi: 10.1152/japplphysiol.00865.2005. Epub 2005 Dec 15.
O-linked N-acetylglucosaminylation (O-GlcNAc) is a regulatory posttranslational modification of nucleocytoplasmic proteins, which consists of the attachment of N-acetylglucosamine to serine or threonine residues of a protein. This glycosylation is a ubiquitous posttranslational modification, which probably plays important roles in many aspects of protein function. Our laboratory has previously reported that, in skeletal muscle, proteins of the glycolytic pathway and energetic metabolism and contractile proteins were O-GlcNAc modified (Cieniewski-Bernard C, Bastide B, Lefebvre T, Lemoine J, Mounier Y, and Michalski JC. Mol Cell Proteomics 3: 577-585, 2004). O-GlcNAc has been recently demonstrated to play a role in modulating cellular function in response to nutrition and also in stress conditions. Therefore, we have investigated here the implication of the glycosylation/deglycosylation process in the development of atrophy in rat skeletal muscle after hindlimb unloading. The high O-GlcNAc level found in control soleus [compared with control extensor digitorum longus (EDL)] becomes lower in atrophied soleus. On the opposite side, the low rate of O-GlcNAc in control EDL reaches higher levels in EDL, not atrophied after hindlimb unloading. These variations in O-GlcNAc level are correlated with a variation of the O-GlcNAc process enzyme activities and could be associated with a differential expression of heat shock proteins. Our results suggest that O-GlcNAc variations could control the muscle protein homeostasis and be implicated in the regulation of muscular atrophy.
O-连接的N-乙酰葡糖胺化修饰（O-GlcNAc）是一种对核质蛋白进行调控的翻译后修饰，它是将N-乙酰葡糖胺连接到蛋白质的丝氨酸或苏氨酸残基上。这种糖基化是一种普遍存在的翻译后修饰，可能在蛋白质功能的许多方面发挥重要作用。我们实验室之前报道过，在骨骼肌中，糖酵解途径、能量代谢的蛋白质以及收缩蛋白都发生了O-GlcNAc修饰（Cieniewski-Bernard C，Bastide B，Lefebvre T，Lemoine J，Mounier Y，以及Michalski JC。《分子与细胞蛋白质组学》3：577 - 585，2004年）。最近已证明O-GlcNAc在响应营养以及应激条件时对调节细胞功能发挥作用。因此，我们在此研究了糖基化/去糖基化过程在大鼠后肢卸载后骨骼肌萎缩发展中的作用。与对照的趾长伸肌（EDL）相比，对照比目鱼肌中发现的高O-GlcNAc水平在萎缩的比目鱼肌中降低。相反，对照EDL中低水平的O-GlcNAc在EDL中达到更高水平，后肢卸载后该肌肉未萎缩。O-GlcNAc水平的这些变化与O-GlcNAc过程中酶活性的变化相关，并且可能与热休克蛋白的差异表达有关。我们的结果表明，O-GlcNAc的变化可能控制肌肉蛋白质稳态，并参与肌肉萎缩的调节。
