title: ROS stress resets circadian clocks to coordinate pro-survival signals.
abstract: Dysfunction of circadian clocks exacerbates various diseases, in part likely due to impaired stress resistance. It is unclear how circadian clock system responds toward critical stresses, to evoke life-protective adaptation. We identified a reactive oxygen species (ROS), H2O2 -responsive circadian pathway in mammals. Near-lethal doses of ROS-induced critical oxidative stress (cOS) at the branch point of life and death resets circadian clocks, synergistically evoking protective responses for cell survival. The cOS-triggered clock resetting and pro-survival responses are mediated by transcription factor, central clock-regulatory BMAL1 and heat shock stress-responsive (HSR) HSF1. Casein kinase II (CK2) -mediated phosphorylation regulates dimerization and function of BMAL1 and HSF1 to control the cOS-evoked responses. The core cOS-responsive transcriptome includes CK2-regulated crosstalk between the circadian, HSR, NF-kappa-B-mediated anti-apoptotic, and Nrf2-mediated anti-oxidant pathways. This novel circadian-adaptive signaling system likely plays fundamental protective roles in various ROS-inducible disorders, diseases, and death.
authors: Department of Physiology & Advanced Research Center for Medical Science, Toho University School of Medicine, Tokyo, Japan.
authors: Teruya
authors: T
authors: Tamaru
authors: Mitsuru
authors: M
authors: Hattori
authors: Yasuharu
authors: Y
authors: Ninomiya
authors: Genki
authors: G
authors: Kawamura
authors: Guillaume
authors: G
authors: Varès
authors: Kousuke
authors: K
authors: Honda
authors: Durga Prasad
authors: DP
authors: Mishra
authors: Bing
authors: B
authors: Wang
authors: Ivor
authors: I
authors: Benjamin
authors: Paolo
authors: P
authors: Sassone-Corsi
authors: Takeaki
authors: T
authors: Ozawa
authors: Ken
authors: K
authors: Takamatsu
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D002470:Cell Survival; D057906:Circadian Clocks; D018869:Heat-Shock Response; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D017382:Reactive Oxygen Species; D047390:Casein Kinase II