PMID- 15913451
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20181201
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 390
IP  - Pt 3
DP  - 2005 Sep 15
TI  - PKCdelta mediates up-regulation of NOX1, a catalytic subunit of NADPH oxidase, 
      via transactivation of the EGF receptor: possible involvement of PKCdelta in 
      vascular hypertrophy.
PG  - 761-7
AB  - NADPH oxidase is the major source of superoxide production in cardiovascular 
      tissues. We reported previously that PG (prostaglandin) F2alpha caused 
      hypertrophy of vascular smooth muscle cells by induction of NOX1, a catalytic 
      subunit of NADPH oxidase. PGF2alpha-induced NOX1 expression was mediated by 
      transactivation of the EGF (epidermal growth factor) receptor and subsequent 
      activation of ERK (extracellular-signal-regulated kinase) 1/2, PI3K 
      (phosphoinositide 3-kinase) and ATF-1 (activating transcription factor-1), a 
      member of the CREB (cAMP-response-element-binding protein)/ATF family. As the 
      receptor for PGF2alpha is known to activate PKC (protein kinase C), involvement 
      of PKC in up-regulation of NOX1 expression was investigated in A7r5 cells. 
      GF109203x, a non-selective inhibitor of PKC, dose-dependently suppressed the 
      induction of NOX1 mRNA by PGF2alpha. Whereas an inhibitor of the conventional 
      PKC, Go 6976, and a PKCeta translocation-inhibitor peptide had no effect, an 
      inhibitor of PKCdelta, rottlerin, significantly attenuated the PGF2alpha-induced 
      increase in NOX1 mRNA. Gene silencing of PKCdelta by RNA interference 
      significantly suppressed the PGF2alpha-induced increase in NOX1 mRNA, as well as 
      phosphorylation of the EGF receptor, ERK1/2 and ATF-1. Silencing of the PKCdelta 
      gene also attenuated the PDGF (platelet-derived growth factor)- induced increase 
      in NOX1 mRNA and transactivation of the EGF receptor. Moreover, the augmented 
      synthesis of the protein induced by PGF2alpha or PDGF was abolished by gene 
      silencing of PKCdelta. These results suggest that PKCdelta-mediated 
      transactivation of the EGF receptor is elicited not only by PGF2alpha, but also 
      by PDGF, and that the subsequent activation of ERK1/2 and ATF-1 leads to 
      up-regulation of NOX1 gene expression and ensuing hypertrophy in the vascular 
      cell lineage.
FAU - Fan, Chun Yuan
AU  - Fan CY
AD  - Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 
      602-8566, Japan.
FAU - Katsuyama, Masato
AU  - Katsuyama M
FAU - Yabe-Nishimura, Chihiro
AU  - Yabe-Nishimura C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Acetophenones)
RN  - 0 (Benzopyrans)
RN  - 0 (Carbazoles)
RN  - 0 (Indoles)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 136194-77-9 (Go 6976)
RN  - E29LP3ZMUH (rottlerin)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Acetophenones
MH  - Animals
MH  - Benzopyrans
MH  - Carbazoles
MH  - Catalysis
MH  - Cell Line
MH  - Enzyme Induction
MH  - ErbB Receptors/*genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Silencing
MH  - Hypertrophy/enzymology/genetics/*metabolism
MH  - Indoles
MH  - NADPH Oxidases/biosynthesis/chemistry/*metabolism
MH  - Platelet-Derived Growth Factor/metabolism
MH  - Protein Kinase C-delta/genetics/*metabolism
MH  - Protein Transport
MH  - Rats
MH  - *Transcriptional Activation
PMC - PMC1199669
EDAT- 2005/05/26 09:00
MHDA- 2006/01/19 09:00
PMCR- 2006/03/15
CRDT- 2005/05/26 09:00
PHST- 2005/05/26 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/05/26 09:00 [entrez]
PHST- 2006/03/15 00:00 [pmc-release]
AID - BJ20050287 [pii]
AID - bj3900761 [pii]
AID - 10.1042/BJ20050287 [doi]
PST - ppublish
SO  - Biochem J. 2005 Sep 15;390(Pt 3):761-7. doi: 10.1042/BJ20050287.