University of Sydney, Faculty of Medicine and Health and Charles Perkins Centre, Camperdown, New South Wales, Australia.
Am J Physiol Cell Physiol. 2020 Sep 1;319(3):C533-C540. doi: 10.1152/ajpcell.00305.2020. Epub 2020 Jul 29.
Humans have internal circadian clocks that ensure that important physiological functions occur at specific times of the day. These molecular clocks are regulated at the genomic level and exist in most cells of the body. Multiple circadian resetting cues have been identified, including light, temperature, and food. Recently, oxygen has been identified as a resetting cue, and emerging science indicates that this occurs through interactions at the cellular level between the circadian transcription-translation feedback loop and the hypoxia-inducible pathway (hypoxia-inducible factor; subject of the 2019 Nobel Prize in Physiology or Medicine). This review will cover recently identified relationships between HIF and proteins of the circadian clock. Interactions between the circadian clock and hypoxia could have wide-reaching implications for human diseases, and understanding the molecular mechanisms regulating these overlapping pathways may open up new strategies for drug discovery.
人类有内部生物钟,确保重要的生理功能在一天中的特定时间发生。这些分子钟在基因组水平上受到调节,存在于身体的大多数细胞中。已经确定了多种生物钟重置提示,包括光、温度和食物。最近,氧气被确定为重置提示,新兴科学表明,这是通过生物钟转录-翻译反馈回路和缺氧诱导途径(缺氧诱导因子;2019 年诺贝尔生理学或医学奖的主题)在细胞水平上的相互作用发生的。本综述将介绍最近发现的 HIF 与生物钟蛋白之间的关系。生物钟与缺氧之间的相互作用可能对人类疾病产生广泛影响,而了解调节这些重叠途径的分子机制可能为药物发现开辟新的策略。