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ROS stress resets circadian clocks to coordinate pro-survival signals. PLoS One 2013;8(12):e82006

Date

12/07/2013

Pubmed ID

24312621

Pubmed Central ID

PMC3846904

DOI

10.1371/journal.pone.0082006

Scopus ID

2-s2.0-84891440383   51 Citations

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.

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 K

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Casein Kinase II
Cell Survival
Circadian Clocks
Heat-Shock Response
Mice
NIH 3T3 Cells
Oxidative Stress
Reactive Oxygen Species
Signal Transduction
Transcriptome
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a