In vitro and in vivo Phase Changes of the Mouse Circadian Clock by Oxidative Stress

Abstract

Mammalian circadian rhythms are governed by an endogenous circadian clock system, including the molecular clock works in each cell and tissue. Adaptation of the circadian clock to different environmental stimuli such as light, food, and stress is essential for homeostasis maintenance. However, the influence of oxidative stress on the circadian clock phase is not fully understood 'in vitro' and 'in vivo'. Here, we examined the effects of hydrogen peroxide (H2O2)-induced oxidative stress on the PERIOD2::LUCIFERASE bioluminescence rhythm in mouse embryonic fibroblasts 'in vitro' and in mouse peripheral tissues 'in vivo'. The circadian clock phase changed with the dose of H2O2 and time of day 'in vitro'; similar phase changes were observed 'in vivo' in the circadian clocks of the peripheral tissues. In addition, mice treated with hemin-induced oxidative stress also showed phase changes of peripheral clocks, similarly as H2O2 treatment. Thus, oxidative stress can entrain circadian clock systems.

Keywords

• Period2, liver, kidney, in vivo imaging, hydrogen peroxide