中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2015, 27(11): 1403-1408
O-GlcNAc修饰调节生物节律研究进展
麻砚涛,罗浑金,靳 倩,张树菊,李家大*
(中南大学生命科学学院医学遗传学国家重点实验室,长沙 410078)
摘 要:生物体的睡眠/ 觉醒、进食等行为以及各种生理、生化、代谢过程都遵循着大约24 h 的周期性变化,称为昼夜节律(circadian rhythms)。昼夜节律与能量代谢之间存在着紧密的联系。位于下丘脑视交叉上核(suprachiasmatic nuclei, SCN) 的中枢生物钟与外周组织细胞中的生物钟共同组成了哺乳动物的昼夜节律系统。以CLOCK/BMAL1 异二聚体为核心的转录/ 翻译负反馈环保障了节律系统的正常运行。各种蛋白质翻译后修饰参与了昼夜节律的调控。综述了氧连β-N- 乙酰葡糖胺修饰(O-GlcNAcylation) 在调节昼夜节律中发挥的重要作用。O-GlcNAc 修饰可以增强一些生物钟蛋白的稳定性及转录活性,也可以影响其他一些生物钟蛋白的磷酸化及细胞定位。抑制生物钟蛋白的O-GlcNAc 修饰导致细胞节律衰弱和多种节律基因表达下调。研究表明,O-GlcNAc 作为机体能量代谢的感受器参与了多条细胞代谢相关信号转导通路的调节,O-GlcNAc 修饰为能量代谢影响昼夜节律提供了一条新的途径。
 
Roles of O-GlcNAcylation on the regulation of circadian rhythms
MA Yan-Tao, LUO Hun-Jin, JIN Qian, ZHANG Shu-ju, LI Jia-Da*
( State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China)
Abstract: Various physiological, biochemical and metabolic processes and behaviors show a circadian rhythm of about 24 hours. There is a close relationship between circadian rhythms and metabolism. In mammals, the circadian system is organized in a highly hierarchical architecture, composed of a central pacemaker in the brain’s suprachiasmatic nuclei (SCN) and subsidiary clocks in peripheral organs. Transcription/translation negative feedback loops involving CLOCK/BMAL1 heterodimer are considered as the prime molecular mechanism sustaining intracellular rhythms. Post-translational modifications play important roles in regulating circadian core proteins. Here, we review that core clock proteins are modified with an O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation of clock proteins may modulate the stabilities, transcriptional activities, phosphorylation and cellular location. Conversely, inhibition of O-GlcNAcylation results in damped circadian rhythms of clock gene expression. As O-GlcNAcylation is sensitive to the glucose level, such modification may provide a new mechanism linking metabolism to circadian rhythms.
 
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