PMID- 16598755
OWN - NLM
STAT- MEDLINE
DCOM- 20061207
LR  - 20161124
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 98
IP  - 6
DP  - 2006 Aug 15
TI  - CREB-dependent cyclooxygenase-2 and microsomal prostaglandin E synthase-1 
      expression is mediated by protein kinase C and calcium.
PG  - 1653-66
AB  - Cellular production of prostaglandins (PGs) is controlled by the concerted 
      actions of cyclooxygenases (COX) and terminal PG synthases on arachidonic acid in 
      response to agonist stimulation. Recently, we showed in an ileal epithelial cell 
      line (IEC-18), angiotensin II-induced COX-2-dependent PGI2 production through 
      p38MAPK, and calcium mobilization (J. Biol. Chem. 280: 1582-1593, 2005). Agonist 
      binding to the AT1 receptor results in activation of PKC activity and Ca2+ 
      signaling but it is unclear how each pathway contributes to PG production. IEC-18 
      cells were stimulated with either phorbol-12,13-dibutyrate (PDB), thapsigargin 
      (TG), or in combination. The PG production and COX-2 and PG synthase expression 
      were measured. Surprisingly, PDB and TG produced PGE2 but not PGI2. This 
      corresponded to induction of COX-2 and mPGES-1 mRNA and protein. PGIS mRNA and 
      protein levels did not change. Activation of PKC by PDB resulted in the 
      activation of ERK1/2, JNK, and CREB whereas activation of Ca2+ signaling by TG 
      resulted in the delayed activation of ERK1/2. The combined effect of PKC and Ca2+ 
      signaling were prolonged COX-2 and mPGES-1 mRNA and protein expression. 
      Inhibition of PKC activity, MEK activity, or Ca2+ signaling blocked agonist 
      induction of COX-2 and mPGES-1. Expression of a dominant negative CREB (S133A) 
      blocked PDB/TG-dependent induction of both COX-2 and mPGES-1 promoters. Decreased 
      CREB expression by siRNA blocked PDB/TG-dependent expression of COX-2 and mPGES-1 
      mRNA. These findings demonstrate a coordinated induction of COX-2 and mPGES-1 by 
      PDB/TG that proceeds through PKC/ERK and Ca2+ signaling cascades, resulting in 
      increased PGE2 production.
CI  - (c) 2006 Wiley-Liss, Inc.
FAU - Pham, Hung
AU  - Pham H
AD  - Department of Medicine, Division of Digestive Diseases, David Geffen School of 
      Medicine at UCLA, University of California, Los Angeles, California 90095-1786, 
      USA.
FAU - Shafer, Lindsay M
AU  - Shafer LM
FAU - Slice, Lee W
AU  - Slice LW
LA  - eng
GR  - DK061485/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 (RNA, Small Interfering)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - CREB-Binding Protein/*metabolism
MH  - Calcium/*metabolism
MH  - Cell Line
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Dinoprostone/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Intramolecular Oxidoreductases/genetics/*metabolism
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Prostaglandin-E Synthases
MH  - Protein Kinase C/*metabolism
MH  - RNA Stability
MH  - RNA, Small Interfering
MH  - Rats
MH  - Signal Transduction
MH  - Thapsigargin/pharmacology
MH  - Time Factors
MH  - Transfection
EDAT- 2006/04/07 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/04/07 09:00
PHST- 2006/04/07 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/04/07 09:00 [entrez]
AID - 10.1002/jcb.20899 [doi]
PST - ppublish
SO  - J Cell Biochem. 2006 Aug 15;98(6):1653-66. doi: 10.1002/jcb.20899.