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PNAS 104 (40): 15747-15752

Copyright © 2007 by the National Academy of Sciences.


Circadian control by the reduction/oxidation pathway: Catalase represses light-dependent clock gene expression in the zebrafish

Jun Hirayama*, Sehyung Cho{dagger}, and Paolo Sassone-Corsi*,{ddagger}

*Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697; and {dagger}Kyung Hee Institute of Age-Related and Brain Diseases, Kyung University, Seoul 130-701, Korea

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved August 7, 2007

Received for publication June 15, 2007.

Abstract: Light is the key entraining stimulus for the circadian clock, but several features of the signaling pathways that convert the photic signal to clock entrainment remain to be deciphered. Here, we show that light induces the production of hydrogen peroxide (H2O2) that acts as the second messenger coupling photoreception to the zebrafish circadian clock. Treatment of light-responsive Z3 cells with H2O2 triggers the induction of zCry1a and zPer2 genes and the subsequent circadian oscillation of zPer1. Remarkably, the induction kinetics and oscillation profile in response to H2O2 are identical to those initiated by light. Catalase (Cat), an antioxidant enzyme degrading H2O2, shows an oscillating pattern of expression and activity, antiphasic to zCry1a and zPer2. Interestingly, overexpression of zCAT results in a reduced light-dependent zCry1a and zPer2 gene induction. In contrast, inhibition of zCAT function enhances light-mediated inducibility of these clock genes. These findings implicate the enzymatic function of zCAT enzyme in the negative regulation of light-dependent clock gene transcriptional activation. Our findings provide an attractive link between the regulation of the cellular reduction/oxidation (redox) state and the photic signaling pathways implicated in circadian control.

Key Words: light signaling • hydrogen peroxide • transcription • circadian rhythms

Author contributions: J.H. and P.S.-C. designed research; J.H. and S.C. performed research; J.H., S.C., and P.S.-C. analyzed data; and J.H. and P.S.-C. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

{ddagger}To whom correspondence should be addressed. E-mail: psc{at}

© 2007 by The National Academy of Sciences of the USA

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