Department of Medical Laboratory, Weifang Medical University, Weifang, 261053, China.
Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Acta Pharmacol Sin. 2023 Jan;44(1):8-18. doi: 10.1038/s41401-022-00934-2. Epub 2022 Jul 11.
O-GlcNAcylation is a post-translational modification of protein in response to genetic variations or environmental factors, which is controlled by two highly conserved enzymes, i.e. O-GlcNAc transferase (OGT) and protein O-GlcNAcase (OGA). Protein O-GlcNAcylation mainly occurs in the cytoplasm, nucleus, and mitochondrion, and it is ubiquitously implicated in the development of cardiovascular disease (CVD). Alterations of O-GlcNAcylation could cause massive metabolic imbalance and affect cardiovascular function, but the role of O-GlcNAcylation in CVD remains controversial. That is, acutely increased O-GlcNAcylation is an adaptive heart response, which temporarily protects cardiac function. While it is harmful to cardiomyocytes if O-GlcNAcylation levels remain high in chronic conditions or in the long run. The underlying mechanisms include regulation of transcription, energy metabolism, and other signal transduction reactions induced by O-GlcNAcylation. In this review, we will focus on the interactions between protein O-GlcNAcylation and CVD, and discuss the potential molecular mechanisms that may be able to pave a new avenue for the treatment of cardiovascular events.
O-糖基化是一种蛋白质的翻译后修饰，可响应遗传变异或环境因素，由两种高度保守的酶，即 O-连接的 N-乙酰氨基葡萄糖转移酶（OGT）和蛋白 O-GlcNAcase（OGA）控制。蛋白质 O-糖基化主要发生在细胞质、细胞核和线粒体中，广泛参与心血管疾病（CVD）的发生发展。O-糖基化的改变可能导致大量代谢失衡，并影响心血管功能，但 O-糖基化在 CVD 中的作用仍存在争议。也就是说，急性增加的 O-糖基化是一种适应性的心脏反应，暂时保护心脏功能。而如果在慢性条件或长期情况下 O-糖基化水平持续升高，则对心肌细胞有害。其潜在机制包括 O-糖基化诱导的转录、能量代谢和其他信号转导反应的调节。在这篇综述中，我们将重点讨论蛋白质 O-糖基化与 CVD 之间的相互作用，并讨论可能为心血管事件治疗开辟新途径的潜在分子机制。
