Journal article
Selenium is a modulator of circadian clock that protects mice from the toxicity of a chemotherapeutic drug via upregulation of the core clock protein, BMAL1
Oncotarget, Vol.2(12), pp.1279-1290
12/31/2011
DOI: 10.18632/oncotarget.411
PMCID: PMC3282084
PMID: 22249125
Abstract
Selenium compounds are known as cancer preventive agents and are also able to ameliorate the toxicity associated with anti-cancer radiation and chemotherapy in mouse models. Sensitivity to the toxicity of chemotherapy is also modulated by the circadian clock, molecular time-keeping system that underlie daily fluctuations in multiple physiological and biochemical processes. Here we show that these two mechanisms are interconnected. By screening a library of small molecules in a cell-based reporter system, we identified L-methyl-selenocysteine as a positive regulator of the core clock protein, BMAL1. L-methyl-selenocysteine up-regulates BMAL1 at the transcriptional level both in cultured cells and in mice. We also show that in tissue culture selenium exerts its action by interfering with TIEG1-mediated repression of
Bmal1
promoter. Selenium treatment fails to protect BMAL1-deficient mice from toxicity induced by the chemotherapeutic agent cyclophosphamide but does protect
Clock
mutant mice deficient in circadian rhythm control but having normal BMAL1. These findings define selenium as circadian modulator and indicate that the tissue protective effect of selenium results, at least in part, from up-regulation of BMAL1 expression and subsequent enhancement of CLOCK/BMAL1-mediated transcription.
Details
- Title: Subtitle
- Selenium is a modulator of circadian clock that protects mice from the toxicity of a chemotherapeutic drug via upregulation of the core clock protein, BMAL1
- Creators
- Yan Hu - Roswell Park Cancer InstituteMary L. Spengler - Roswell Park Cancer InstituteKaren K. Kuropatwinski - Roswell Park Cancer InstituteMaria Comas - Roswell Park Cancer InstituteMarilyn Jackson - Roswell Park Cancer InstituteMikhail V. Chernov - Roswell Park Cancer InstituteAnatoly S. Gleiberman - Roswell Park Cancer InstituteNatalia Fedtsova - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer InstituteAndrei V. Gudkov - Roswell Park Cancer InstituteMarina P. Antoch - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.2(12), pp.1279-1290
- DOI
- 10.18632/oncotarget.411
- PMID
- 22249125
- PMCID
- PMC3282084
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- Impact Journals LLC
- Language
- English
- Date published
- 12/31/2011
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359582102771
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