Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto-SP, Brazil.
Clin Sci (Lond). 2012 Oct;123(8):473-86. doi: 10.1042/CS20110638.
O-GlcNAcylation is an unusual form of protein glycosylation, where a single-sugar [GlcNAc (N-acetylglucosamine)] is added (via β-attachment) to the hydroxyl moiety of serine and threonine residues of nuclear and cytoplasmic proteins. A complex and extensive interplay exists between O-GlcNAcylation and phosphorylation. Many phosphorylation sites are also known glycosylation sites, and this reciprocal occupancy may produce different activities or alter the stability in a target protein. The interplay between these two post-translational modifications is not always reciprocal, as some proteins can be concomitantly phosphorylated and O-GlcNAcylated, and the adjacent phosphorylation or O-GlcNAcylation can regulate the addition of either moiety. Increased cardiovascular production of ROS (reactive oxygen species), termed oxidative stress, has been consistently reported in various chronic diseases and in conditions where O-GlcNAcylation has been implicated as a contributing mechanism for the associated organ injury/protection (for example, diabetes, Alzheimer's disease, arterial hypertension, aging and ischaemia). In the present review, we will briefly comment on general aspects of O-GlcNAcylation and provide an overview of what has been reported for this post-translational modification in the cardiovascular system. We will then specifically address whether signalling molecules involved in redox signalling can be modified by O-GlcNAc (O-linked GlcNAc) and will discuss the critical interplay between O-GlcNAcylation and ROS generation. Experimental evidence indicates that the interactions between O-GlcNAcylation and oxidation of proteins are important not only for cell regulation in physiological conditions, but also under pathological states where the interplay may become dysfunctional and thereby exacerbate cellular injury.
O-糖基化是一种不寻常的蛋白质糖基化形式，其中单个糖[GlcNAc（N-乙酰葡萄糖胺）]通过β-连接（β-attachment）添加到核和细胞质蛋白的丝氨酸和苏氨酸残基的羟基部分。O-糖基化和磷酸化之间存在复杂而广泛的相互作用。许多磷酸化位点也是已知的糖基化位点，这种相互占据可能产生不同的活性或改变靶蛋白的稳定性。这两种翻译后修饰之间的相互作用并不总是相互的，因为一些蛋白质可以同时被磷酸化和 O-糖基化，并且相邻的磷酸化或 O-糖基化可以调节任何部分的添加。在各种慢性疾病和 O-糖基化被认为是相关器官损伤/保护的潜在机制的情况下，心血管系统中 ROS（活性氧）的产生增加，称为氧化应激，已经得到了一致的报道（例如，糖尿病、阿尔茨海默病、动脉高血压、衰老和缺血）。在本综述中，我们将简要评论 O-糖基化的一般方面，并概述在心血管系统中已报道的这种翻译后修饰。然后，我们将特别讨论参与氧化还原信号转导的信号分子是否可以被 O-GlcNAc（O-连接的 GlcNAc）修饰，并讨论 O-糖基化和 ROS 生成之间的关键相互作用。实验证据表明，O-糖基化和蛋白质氧化之间的相互作用不仅对生理条件下的细胞调节很重要，而且在病理状态下也很重要，在这种情况下，相互作用可能变得功能失调，从而加剧细胞损伤。
