PMID- 18461556
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20240312
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 105
IP  - 1
DP  - 2008 Sep 1
TI  - Prostaglandin F2alpha induces the normoxic activation of the hypoxia-inducible 
      factor-1 transcription factor in differentiating 3T3-L1 preadipocytes: Potential 
      role in the regulation of adipogenesis.
PG  - 89-98
LID - 10.1002/jcb.21801 [doi]
AB  - Prostaglandin F2alpha (PGF2alpha) is a potent paracrine inhibitor of adipocyte 
      differentiation. Here we show that treatment of differentiating 3T3-L1 
      preadipocytes with PGF2alpha induces the expression of DEC1, a transcriptional 
      repressor that has previously been implicated in the inhibition of adipogenesis 
      in response to hypoxia as a downstream effector of the hypoxia-inducible factor-1 
      (HIF-1) transcription factor. Surprisingly, despite performing our experiments 
      under normal ambient oxygen conditions, we find that treatment of differentiating 
      3T3-L1 preadipocytes with PGF2alpha also results in the marked activation of 
      HIF-1, as measured by an increase in the accumulation of the HIF-1alpha 
      regulatory subunit. However, unlike the effects of hypoxia, this 
      PGF2alpha-induced normoxic increase in HIF-1alpha is not mediated by an increase 
      in the stability of the HIF-1alpha polypeptide, rather we find that PGF2alpha 
      selectively increases the expression of the alternatively spliced HIF-1alpha I.1 
      mRNA isoform. Significantly, we demonstrate that the shRNA-mediated knockdown of 
      endogenous HIF-1alpha expression attenuates the PGF2alpha-induced expression of 
      DEC1, overcomes the inhibitory effects of PGF2alpha on the expression of 
      proadipogenic transcription factors C/EBPalpha and PPARgamma and partially 
      rescues the PGF2alpha-induced inhibition of adipogenesis. Taken together, these 
      results indicate that PGF2alpha promotes the activation of the HIF-1 
      transcription factor pathway under normal oxygen conditions, and highlight a 
      potential role for the normoxic activation of the HIF-1/DEC1-pathway in mediating 
      the inhibitory effects of PGF2alpha on adipocyte differentiation.
CI  - (c) 2008 Wiley-Liss, Inc.
FAU - Liu, Li
AU  - Liu L
AD  - Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern 
      University, 303 E. Chicago Ave. Chicago, Illinois 60611, USA.
FAU - Clipstone, Neil A
AU  - Clipstone NA
LA  - eng
GR  - R01 DK063298/DK/NIDDK NIH HHS/United States
GR  - R01 DK063298-04/DK/NIDDK NIH HHS/United States
GR  - DK-63298/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Peptides)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - B7IN85G1HY (Dinoprost)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adipocytes/*cytology/drug effects/*metabolism
MH  - Adipogenesis/*drug effects
MH  - Animals
MH  - Cell Line
MH  - Dinoprost/*pharmacology
MH  - Exons/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Mice
MH  - Oxygen/*metabolism
MH  - Peptides/metabolism
MH  - Protein Subunits/metabolism
MH  - RNA Interference
MH  - RNA, Messenger/genetics
MH  - Transcription, Genetic/drug effects/genetics
PMC - PMC2634301
MID - NIHMS82252
EDAT- 2008/05/08 09:00
MHDA- 2008/10/28 09:00
PMCR- 2009/02/02
CRDT- 2008/05/08 09:00
PHST- 2008/05/08 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/05/08 09:00 [entrez]
PHST- 2009/02/02 00:00 [pmc-release]
AID - 10.1002/jcb.21801 [doi]
PST - ppublish
SO  - J Cell Biochem. 2008 Sep 1;105(1):89-98. doi: 10.1002/jcb.21801.