PMID- 21668646
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20141120
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 278
IP  - 16
DP  - 2011 Aug
TI  - Novel suppression mechanism operating in early phase of adipogenesis by positive 
      feedback loop for enhancement of cyclooxygenase-2 expression through 
      prostaglandin F2alpha receptor mediated activation of MEK/ERK-CREB cascade.
PG  - 2901-12
LID - 10.1111/j.1742-4658.2011.08213.x [doi]
AB  - Prostaglandin (PG) F(2alpha) suppresses adipocyte differentiation by inhibiting the 
      function of peroxisome proliferator-activated receptor gamma. In this study, we 
      identified a novel suppression mechanism, operating in the early phase of 
      adipogenesis, that increased the production of anti-adipogenic PGF(2alpha) and PGE(2) 
      by enhancing cyclooxygenase (COX) 2 expression through the PGF(2alpha) -activated FP 
      receptor/extracellular-signal-regulated kinase (ERK)/cyclic AMP response element 
      binding protein (CREB) cascade. COX-2 expression was enhanced with a peak at 1 h 
      for the mRNA level and at 3 h for the protein level after the addition of 
      Fluprostenol, an FP receptor agonist. The Fluprostenol-derived elevation of COX-2 
      expression was suppressed by the co-treatment with an FP receptor antagonist, 
      AL8810, with a mitogen-activated protein kinase (MEK; ERK kinase) inhibitor, 
      PD98059. ERK was phosphorylated within 10 min after the addition of Fluprostenol, 
      and its phosphorylation was inhibited by the co-treatment with AL8810 or PD98059. 
      Moreover, FP receptor mediated activation of the MEK/ERK cascade and COX-2 
      expression increased the production of PGF(2alpha) and PGE(2) . An FP receptor 
      antagonist and each inhibitor for MEK and COX-2 suppressed the PGF(2alpha) -derived 
      induction of synthesis of these PGs. Furthermore, promoter-luciferase and 
      chromatin immunoprecipitation assays demonstrated that PGF(2alpha) -derived COX-2 
      expression was activated through binding of CREB to the promoter region of the 
      COX-2 gene in 3T3-L1 cells. These results indicate that PGF(2alpha) suppresses the 
      progression of the early phase of adipogenesis by enhancing the binding of CREB 
      to the COX-2 promoter via FP receptor activated MEK/ERK cascade. Thus, PGF(2alpha) 
      forms a positive feedback loop that coordinately suppresses the early phase of 
      adipogenesis through the increased production of anti-adipogenic PGF(2alpha) and 
      PGE(2) .
CI  - (c) 2011 The Authors Journal compilation (c) 2011 FEBS.
FAU - Ueno, Toshiyuki
AU  - Ueno T
AD  - Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical 
      Sciences, Japan.
FAU - Fujimori, Ko
AU  - Fujimori K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110628
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (PPAR gamma)
RN  - 0 (Prostaglandins F, Synthetic)
RN  - 0 (Receptors, Prostaglandin)
RN  - 0 (prostaglandin F2alpha receptor)
RN  - 358S7VUE5N (fluprostenol)
RN  - B7IN85G1HY (Dinoprost)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipogenesis/*drug effects
MH  - Animals
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Cyclooxygenase 2/*genetics
MH  - Dinoprost/biosynthesis
MH  - Dinoprostone/biosynthesis
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - Feedback
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - PPAR gamma/metabolism
MH  - Prostaglandins F, Synthetic/pharmacology
MH  - Receptors, Prostaglandin/*physiology
MH  - Signal Transduction/physiology
EDAT- 2011/06/15 06:00
MHDA- 2011/10/04 06:00
CRDT- 2011/06/15 06:00
PHST- 2011/06/15 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
AID - 10.1111/j.1742-4658.2011.08213.x [doi]
PST - ppublish
SO  - FEBS J. 2011 Aug;278(16):2901-12. doi: 10.1111/j.1742-4658.2011.08213.x. Epub 
      2011 Jun 28.