ROS stress resets circadian clocks to coordinate pro-survival signals. PLoS One 2013;8(12):e82006
Date
12/07/2013Pubmed ID
24312621Pubmed Central ID
PMC3846904DOI
10.1371/journal.pone.0082006Scopus ID
2-s2.0-84891440383 (requires institutional sign-in at Scopus site) 82 CitationsAbstract
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.
Author List
Tamaru T, Hattori M, Ninomiya Y, Kawamura G, Varès G, Honda K, Mishra DP, Wang B, Benjamin I, Sassone-Corsi P, Ozawa T, Takamatsu KAuthor
Ivor J. Benjamin MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCasein Kinase II
Cell Survival
Circadian Clocks
Heat-Shock Response
Mice
NIH 3T3 Cells
Oxidative Stress
Reactive Oxygen Species
Signal Transduction
Transcriptome
