Display Settings:

Format

Send to:

Choose Destination
J Biol Chem. 2009 Apr 17;284(16):10601-9. doi: 10.1074/jbc.M808742200. Epub 2009 Feb 23.

Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion.

Author information

  • 1Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Institute of Genetic Science, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, Yonsei University, Seoul 120-752, Korea.

Abstract

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.

PMID:
19237544
[PubMed - indexed for MEDLINE]
PMCID:
PMC2667747
Free PMC Article

Images from this publication.See all images (7)Free text

FIGURE 1.
FIGURE 2.
FIGURE 3.
FIGURE 4.
FIGURE 5.
FIGURE 6.
FIGURE 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk