Circadian oscillation expression of ornithine carbamoyltransferase and its significance in sleep disturbance

• Published in: Biochemical and biophysical research communications 2021-06, Vol.559, p.217-221
• Main Authors: Wang, Wei, Zhang, Yifan, Ding, Mengnan, Huang, Xin, Zhang, Min, Gu, Yu, Wu, Lin, Zhang, Chongchong, Lu, Chunfeng, Shen, Beifen, Xing, Chen, Song, Lun
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Circadian clock; Circadian Rhythm; Gene Expression Regulation, Enzymologic; Hep G2 Cells; Homeostasis; Humans; Liver - enzymology; Male; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism; Ornithine Carbamoyltransferase - genetics; Ornithine Carbamoyltransferase - metabolism; OTC; Rats; Rats, Sprague-Dawley; RORa; Sleep - genetics; Sleep deprivation; Sleep disturbance; Sleep Wake Disorders - enzymology; Sleep Wake Disorders - genetics; Sleep Wake Disorders - physiopathology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.04.100

Ornithine transcarbamylases (OTC), a key enzyme in urea cycle, is an important marker for some liver injury or diseases. However, whether OTC could be a sensitive indicator for liver dysfunction under sleep disturbance condition remains unknown. The present study aimed to explore the circadian oscillation expression of OTC and its significance in disturbed sleep condition. Sleep disturbance was conducted by a sleep deprivation (SD) instrument. Our results found that SD for 72h induced abnormal increasing of OTC levels in serum and liver of rats. And, serum OTC concentration and liver OTC expression could return to normal levels after recovery sleep following SD. Moreover, hepatic OTC expression showed circadian oscillation in day and night, characterized with occurrence of a peak between ZT 22 and ZT 2, and a nadir between ZT 14 and ZT 18. Further analysis suggested the existence of ROR response element (RORE) for potential RORɑ binding sites in OTC promoter region, and elevated RORɑ expression in rat livers under sleep disturbance condition. Additionally, oscillation expression of OTC induced by serum shock in HepG2 cells was characterized with a peak occurred between ZT 12 and ZT 16, and RORɑ knockdown at ZT 16 significantly lowered OTC expression. The results together indicate that OTC is closely correlated with circadian clock, and could be a sensitive indicator for sleep disturbance stress. •Sleep disturbance induced abnormal increasing of circulating and liver OTC.•Abnormal induction of OTC could return to normal level after recovery sleep following sleep disturbance.•OTC could be a sensitive indicator for sleep disturbance stress.•OTC expression in liver was characterized with circadian fluctuation.•The oscillation expression of OTC was regulated by RORa.