Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 145, Issue -, Pages 312-320Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2019.09.036
Keywords
H2O2; Circadian rhythm; REV-ERB alpha/beta; STAT3; PRX2; BMAL1; Bioluminescence
Funding
- National Natural Science Foundation of China [31401010, 81773930]
- Foundation of China Space Medicine Engineering Advanced Research [2015SY54A0501]
- Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center [SMFA17A03]
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The circadian rhythm is a widespread physiological phenomenon present in almost all forms of life and is constituted by a system of interlocked transcriptional/translational feedback loops (TTFLs). External zeitgebers regulate biological rhythms through the direct or indirect regulation of circadian genes. Oxidative stress is involved in many diseases and injuries, such as ageing, diabetes, Alzheimer's disease, and cancer. Despite an increasing number of studies on circadian rhythm disorders caused by oxidative stress, little is known about the effects of oxidants on clock gene expression and the underlying mechanism. In this study, we found that the protein expression of circadian genes Clock, Bmal1, Per1/2, and Cty1/2 in NIH3T3 cells was upregulated by hydrogen peroxide (H2O2), an important mediator of oxidative stress. In addition, H2O2 modulated the circadian rhythm of Bmall-luciferase via RORa, REV-ERB alpha (NR1D1), and REV-ERBO (NR1D2). Further studies showed that H2O2 regulated biological rhythm by PRX2-STAT3-REV-ERB alpha/beta pathway. These findings provide an accessory loop-related mechanism by which non-transcriptional oscillation interplays with TTFLs.
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