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  2. Hydrogen peroxide modulates clock gene expression via PRX2-STAT3-REV-ERBα/β pathway

Hydrogen peroxide modulates clock gene expression via PRX2-STAT3-REV-ERBα/β pathway

  • Free Radic Biol Med. 2019 Dec;145:312-320. doi: 10.1016/j.freeradbiomed.2019.09.036.
Guohua Ji 1 Ke Lv 1 Hailong Chen 1 Yanli Wang 1 Yongliang Zhang 1 Yinghui Li 1 Lina Qu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 26 Beiqing Road, Beijing, 100094, PR China.
  • 2 State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 26 Beiqing Road, Beijing, 100094, PR China. Electronic address: linaqu@263.net.
Abstract

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 Cry1/2 in NIH3T3 cells was upregulated by hydrogen peroxide (H2O2), an important mediator of oxidative stress. In addition, H2O2 modulated the circadian rhythm of Bmal1-luciferase via RORα, REV-ERBα (NR1D1), and REV-ERBβ (NR1D2). Further studies showed that H2O2 regulated biological rhythm by PRX2-STAT3-REV-ERBα/β pathway. These findings provide an accessory loop-related mechanism by which non-transcriptional oscillation interplays with TTFLs.

Keywords

BMAL1; Bioluminescence; Circadian rhythm; H(2)O(2); PRX2; REV-ERBα/β; STAT3.

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