PMID- 24072780
OWN - NLM
STAT- MEDLINE
DCOM- 20140226
LR  - 20211203
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 28
IP  - 1
DP  - 2014 Jan
TI  - Inhibition of protein translation as a novel mechanism for prostaglandin E2 
      regulation of cell functions.
PG  - 56-66
LID - 10.1096/fj.13-231720 [doi]
AB  - Prostaglandin E2 (PGE2) regulates numerous biological processes by modulating 
      transcriptional activation, epigenetic control, proteolysis, and secretion of 
      various proteins. Scar formation depends on fibroblast elaboration of matrix 
      proteins such as collagen, and this process is strongly suppressed by PGE2 
      through activation of cAMP-dependent protein kinase A (PKA). However, the actual 
      mechanism by which PGE2-PKA signaling inhibits collagen expression in fibroblasts 
      has never been delineated, and that was the objective of this study. PGE2 
      unexpectedly induced a rapid reduction in procollagen I protein expression in 
      adult lung fibroblasts, with a half-maximum effect at 1.5 h. This effect 
      reflected its inhibition of translation rather than transcription. Global protein 
      synthesis was also inhibited by PGE2. This action was mediated by PKA and 
      involved both activation of ribosomal protein (rpS6) and suppression of mammalian 
      target of rapamycin (mTOR). Similar effects of PGE2 were demonstrated in mouse 
      peritoneal macrophages (PMs). These findings identify inhibition of translation 
      as a new mechanism by which PGE2 regulates cellular function and a novel example 
      of translational inhibition mediated by opposing actions on two distinct 
      translational control pathways. Translational inhibition would be expected to 
      contribute to dynamic alterations in cell function that accompany the changing 
      PGE2 levels observed in disease states and with various pharmacotherapies.
FAU - Okunishi, Katsuhide
AU  - Okunishi K
AD  - 26301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-5642. 
      petersm@umich.edu.
FAU - DeGraaf, Angela J
AU  - DeGraaf AJ
FAU - Zaslona, Zbigniew
AU  - Zaslona Z
FAU - Peters-Golden, Marc
AU  - Peters-Golden M
LA  - eng
GR  - R01 HL094311/HL/NHLBI NIH HHS/United States
GR  - HL094311/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130926
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Collagen Type I)
RN  - 0 (Ribosomal Protein S6)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Collagen Type I/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Dinoprostone/*metabolism
MH  - Fibroblasts/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Lung/cytology/metabolism
MH  - Macrophages, Peritoneal/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - Protein Transport/physiology
MH  - RNA Interference
MH  - Ribosomal Protein S6/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3868831
OTO - NOTNLM
OT  - fibroblasts
OT  - macrophages
OT  - mammalian target of rapamycin
OT  - protein kinase A
OT  - ribosomal protein S6
EDAT- 2013/09/28 06:00
MHDA- 2014/02/27 06:00
PMCR- 2015/01/01
CRDT- 2013/09/28 06:00
PHST- 2013/09/28 06:00 [entrez]
PHST- 2013/09/28 06:00 [pubmed]
PHST- 2014/02/27 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - fj.13-231720 [pii]
AID - 13-231720 [pii]
AID - 10.1096/fj.13-231720 [doi]
PST - ppublish
SO  - FASEB J. 2014 Jan;28(1):56-66. doi: 10.1096/fj.13-231720. Epub 2013 Sep 26.