Lefebvre Tony, Dehennaut Vanessa, Guinez Céline, Olivier Stéphanie, Drougat Ludivine, Mir Anne-Marie, Mortuaire Marlène, Vercoutter-Edouart Anne-Sophie, Michalski Jean-Claude
CNRS-UMR 8576, Unit of Structural and Functional Glycobiology, IFR 147, University of Lille 1, Villeneuve d'Ascq, France.
Biochim Biophys Acta. 2010 Feb;1800(2):67-79. doi: 10.1016/j.bbagen.2009.08.008. Epub 2009 Sep 2.
O-GlcNAcylation is widespread within the cytosolic and nuclear compartments of cells. This post-translational modification is likely an indicator of good health since its intracellular level correlates with the availability of extracellular glucose. Apart from its status as a nutrient sensor, O-GlcNAcylation may also act as a stress sensor since it exerts its fundamental effects in response to stress. Several studies report that the cell quickly responds to an insult by elevating O-GlcNAcylation levels and by unmasking a newly described Hsp70-GlcNAc binding property. From a more practical point of view, it has been shown that O-GlcNAcylation impairments contribute to the etiology of cardiovascular diseases, type-2 diabetes and Alzheimer's disease (AD), three illnesses common in occidental societies. Many studies have demonstrated that O-GlcNAcylation operates as a powerful cardioprotector and that by raising O-GlcNAcylation levels, the organism more successfully resists trauma-hemorrhage and ischemia/reperfusion injury. Recent data have also shown that insulin resistance and, more broadly, type-2 diabetes can be controlled by O-GlcNAcylation of the insulin pathway and O-GlcNAcylation of the gluconeogenesis transcription factors FoxO1 and CRCT2. Lastly, the finding that AD may correspond to a type-3 diabetes offers new perspectives into the knowledge of the neuropathology and into the search for new therapeutic avenues.
O-连接的N-乙酰葡糖胺化修饰（O-GlcNAcylation）广泛存在于细胞的胞质和细胞核区室中。这种翻译后修饰可能是身体健康的一个指标，因为其细胞内水平与细胞外葡萄糖的可利用性相关。除了作为一种营养传感器的身份外，O-GlcNAcylation修饰还可能作为一种应激传感器，因为它在应激反应中发挥其基本作用。多项研究报告称，细胞会通过提高O-GlcNAcylation修饰水平以及揭示一种新描述的热休克蛋白70（Hsp70）与GlcNAc的结合特性来快速应对损伤。从更实际的角度来看，已有研究表明，O-GlcNAcylation修饰功能受损会导致心血管疾病、2型糖尿病和阿尔茨海默病（AD）的病因，这三种疾病在西方社会很常见。许多研究表明，O-GlcNAcylation修饰起到强大的心脏保护作用，通过提高O-GlcNAcylation修饰水平，生物体能够更成功地抵抗创伤性出血和缺血/再灌注损伤。最近的数据还表明，胰岛素抵抗以及更广泛的2型糖尿病可以通过胰岛素信号通路的O-GlcNAcylation修饰以及糖异生转录因子叉头框蛋白O1（FoxO1）和CRCT2的O-GlcNAcylation修饰来控制。最后，AD可能相当于3型糖尿病这一发现为神经病理学知识和寻找新治疗途径提供了新的视角。
