Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, KY, United States of America.
Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States of America.
Biochim Biophys Acta Mol Basis Dis. 2020 May 1;1866(5):165712. doi: 10.1016/j.bbadis.2020.165712. Epub 2020 Jan 31.
The post-translational modification of serine and threonine residues of nuclear, cytosolic, and mitochondrial proteins by O-linked β-N-acetyl glucosamine (O-GlcNAc) has long been seen as an important regulatory mechanism in the cardiovascular system. O-GlcNAcylation of cardiac proteins has been shown to contribute to the regulation of transcription, metabolism, mitochondrial function, protein quality control and turnover, autophagy, and calcium handling. In the heart, acute increases in O-GlcNAc have been associated with cardioprotection, such as those observed during ischemia/reperfusion. Conversely, chronic increases in O-GlcNAc, often associated with diabetes and nutrient excess, have been shown to contribute to cardiac dysfunction. Traditionally, many studies have linked changes in O-GlcNAc with nutrient availability and as such O-GlcNAcylation is often seen as a nutrient driven process. However, emerging evidence suggests that O-GlcNAcylation may also be regulated by non-nutrient dependent mechanisms, such as transcriptional and post-translational regulation. Therefore, the goals of this review are to provide an overview of the impact of O-GlcNAcylation in the cardiovascular system, how this is regulated and to discuss the emergence of regulatory mechanisms other than nutrient availability.
丝氨酸和苏氨酸残基的翻译后修饰通过 O-连接的β-N-乙酰葡萄糖胺（O-GlcNAc）在核、胞质和线粒体蛋白中，长期以来一直被视为心血管系统中的重要调节机制。已经表明，心脏蛋白的 O-GlcNAc 化有助于转录、代谢、线粒体功能、蛋白质质量控制和周转、自噬和钙处理的调节。在心脏中，O-GlcNAc 的急性增加与心脏保护有关，如在缺血/再灌注期间观察到的那样。相反，O-GlcNAc 的慢性增加，通常与糖尿病和营养过剩有关，已被证明有助于心脏功能障碍。传统上，许多研究将 O-GlcNAc 的变化与营养供应联系起来，因此 O-GlcNAc 化通常被视为一种营养驱动的过程。然而，新出现的证据表明，O-GlcNAc 化也可能受到非营养依赖机制的调节，例如转录和翻译后调节。因此，本综述的目的是概述 O-GlcNAc 化在心血管系统中的影响、其调节方式，并讨论除营养供应以外的调节机制的出现。
