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Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion

 Haemi Lee  ;  Yoo Jeong Lee  ;  Hyeonjin Choi  ;  Eun Hee Ko  ;  Jae-woo Kim 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.284(16) : 10601-10609, 2009 
Journal Title
Issue Date
3T3-L1 Cells ; Adipocytes/cytology ; Adipocytes/physiology* ; Animals ; Antioxidants/metabolism ; CCAAT-Enhancer-Binding Protein-beta/genetics ; CCAAT-Enhancer-Binding Protein-beta/metabolism ; Cell Differentiation/physiology* ; Cyclin A/metabolism ; DNA/metabolism ; Hydrogen Peroxide/metabolism ; Mice ; Mitosis/physiology* ; Oxidants/metabolism ; Oxidation-Reduction ; Protein Binding ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism* ; Sirtuin 1 ; Sirtuins/genetics ; Sirtuins/metabolism ; Stilbenes/metabolism
Growth-arrested 3T3-L1 preadipocytes rapidly express CCAAT/enhancer-binding protein-beta (C/EBPbeta) upon hormonal induction of differentiation. However, the DNA binding activity of C/EBPbeta is not activated until the cells synchronously reenter S phase during the mitotic clonal expansion (MCE) phase of differentiation. In this period, C/EBPbeta is sequentially phosphorylated by MAPK and glycogen synthase kinase-3beta, inducing C/EBPbeta DNA binding activity and transcription of its target genes. Because the DNA binding activity of C/EBPbeta is further enhanced by oxidation in vitro, we investigated how redox state affects C/EBPbeta DNA binding and MCE during adipogenesis. When 3T3-L1 cells were treated with H(2)O(2) and hormonal stimuli, differentiation was accelerated with increased expression of peroxisome proliferator-activated receptor gamma. Interestingly, cell cycle progression (S to G(2)/M phase) was markedly enhanced by H(2)O(2), whereas antioxidants caused an S phase arrest during the MCE. H(2)O(2) treatment resulted in the early appearance of a punctate pattern observed by immunofluorescent staining of C/EBPbeta, which is a hallmark for C/EBPbeta binding to regulatory elements, whereas a short antioxidant treatment rapidly dispersed the centromeric localization of C/EBPbeta. Consistently, reactive oxygen species production was increased during 3T3-L1 differentiation. Our results indicate that redox-induced C/EBPbeta DNA binding activity, along with the dual phosphorylation of C/EBPbeta, is required for the MCE and terminal differentiation of adipocytes
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
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