Document Detail

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.
MedLine Citation:
PMID:  22753467     Owner:  NLM     Status:  MEDLINE    
The role of the circadian clock in skin and the identity of genes participating in its chronobiology remain largely unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle-related genes, the former peaking during the day and the latter at night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes, because keratinocyte-specific deletion of Bmal1 obliterates time-of-day-dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. In agreement with higher cellular susceptibility to UV-induced DNA damage during S-phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. Because in the human epidermis maximum numbers of keratinocytes go through S-phase in the late afternoon, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation so that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.
Mikhail Geyfman; Vivek Kumar; Qiang Liu; Rolando Ruiz; William Gordon; Francisco Espitia; Eric Cam; Sarah E Millar; Padhraic Smyth; Alexander Ihler; Joseph S Takahashi; Bogi Andersen
Related Documents :
6189747 - Effect of vitamin a acid on homeostasis and differentiation of epidermal cells cultured...
10737547 - Regulation of inducible nitric oxide synthase by dietary phytoestrogen in mcf-7 human m...
20599217 - Concentration of arginine and optimal time of hypertonic saline in restoration of t-cel...
9741367 - Induction of il-8 production in human alveolar macrophages and human bronchial epitheli...
1367057 - Use of recombinant dna technology for engineering mammalian cells to produce proteins.
6968797 - 111indium-labeled human alveolar macrophages and monocytes: function and ultrastructure.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-02
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-10-11     Revised Date:  2014-05-29    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11758-63     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
ARNTL Transcription Factors / genetics,  metabolism*
Cell Cycle / physiology
Cell Proliferation*
Circadian Rhythm / genetics*,  physiology
DNA Damage / genetics*,  physiology
Enzyme-Linked Immunosorbent Assay
Epidermis / cytology*,  radiation effects
Metabolic Networks and Pathways / genetics*,  physiology
Mice, Inbred C57BL
Microarray Analysis
Polymerase Chain Reaction
Transcriptome / genetics*,  physiology
Ultraviolet Rays / adverse effects
Grant Support
AR56439/AR/NIAMS NIH HHS; F32 DA024556/DA/NIDA NIH HHS; P30 CA062203/CA/NCI NIH HHS; R01 AR056439/AR/NIAMS NIH HHS; T32 CA113265/CA/NCI NIH HHS; T32-HD60555/HD/NICHD NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/Arntl protein, mouse; G34N38R2N1/Bromodeoxyuridine; SML2Y3J35T/Colchicine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Modeling individual-level heterogeneity in racial residential segregation.
Next Document:  Evolution of insect arylalkylamine N-acetyltransferases: structural evidence from the yellow fever m...