PMID- 15680482
OWN - NLM
STAT- MEDLINE
DCOM- 20050922
LR  - 20131121
IS  - 0167-0115 (Print)
IS  - 0167-0115 (Linking)
VI  - 127
IP  - 1-3
DP  - 2005 Apr 15
TI  - Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via 
      redox-sensitive mitogen-activated protein kinase (MAPK).
PG  - 159-67
AB  - Oxidative stress is known to be involved in growth control of vascular smooth 
      muscle cells (VSMCs). We and others have demonstrated that angiotensin II (Ang 
      II) has an important role in vascular remodeling. Several reports suggested that 
      VSMC growth induced by Ang II was elicited by oxidative stress. Gax, growth 
      arrest-specific homeobox is a homeobox gene expressed in the cardiovascular 
      system. Over expression of Gax is demonstrated to inhibit VSMC growth. We 
      previously reported that Ang II down-regulated Gax expression. To address the 
      regulatory mechanism of Gax, we investigated the significance of oxidative stress 
      in Ang II-induced suppression of Gax expression. We further examined the 
      involvement of mitogen-activated protein kinases (MAPKs), which is crucial for 
      cell growth and has shown to be activated by oxidative stress, on the regulation 
      of Gax expression by Ang II. Ang II markedly augmented intracellular H2O2 
      production which was decreased by pretreatment with N-acetylcystein (NAC), an 
      anti-oxidant. Ang II and H2O2 decreased Gax expression dose-dependently and these 
      effects were blocked by administration of both NAC and pyrrolidine 
      dithiocarbamate (PDTC), another anti-oxidant. Ang II and H2O2 induced marked 
      activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was 
      blocked by NAC. Ang II and H2O2 also activated p38MAPK, and they were blocked by 
      pre-treatment with NAC. However, the level of activated p38MAPK was quite low in 
      comparison with ERK1/2. Ang II- or H2O2 -induced Gax down-regulation was 
      significantly inhibited by PD98059, an ERK1/2 inhibitor but not SB203580, a 
      p38MAPK inhibitor. The present results demonstrated the significance of 
      regulation of Gax expression by redox-sensitive ERK1/2 activation.
FAU - Saito, Takatoshi
AU  - Saito T
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
FAU - Itoh, Hiroshi
AU  - Itoh H
FAU - Yamashita, Jun
AU  - Yamashita J
FAU - Doi, Kentaro
AU  - Doi K
FAU - Chun, Tae-Hwa
AU  - Chun TH
FAU - Tanaka, Tokuji
AU  - Tanaka T
FAU - Inoue, Mayumi
AU  - Inoue M
FAU - Masatsugu, Ken
AU  - Masatsugu K
FAU - Fukunaga, Yasutomo
AU  - Fukunaga Y
FAU - Sawada, Naoki
AU  - Sawada N
FAU - Sakaguchi, Satsuki
AU  - Sakaguchi S
FAU - Arai, Hiroshi
AU  - Arai H
FAU - Tojo, Katsuyoshi
AU  - Tojo K
FAU - Tajima, Naoko
AU  - Tajima N
FAU - Hosoya, Tatsuo
AU  - Hosoya T
FAU - Nakao, Kazuwa
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Meox2 protein, rat)
RN  - 0 (Muscle Proteins)
RN  - 0 (Oxidants)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 11128-99-7 (Angiotensin II)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - *Gene Expression Regulation
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Muscle Proteins/genetics/*metabolism
MH  - Muscle, Smooth, Vascular/cytology
MH  - Myocytes, Smooth Muscle/cytology/metabolism
MH  - Oxidants/metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
EDAT- 2005/02/01 09:00
MHDA- 2005/09/24 09:00
CRDT- 2005/02/01 09:00
PHST- 2004/05/02 00:00 [received]
PHST- 2004/10/29 00:00 [revised]
PHST- 2004/11/18 00:00 [accepted]
PHST- 2005/02/01 09:00 [pubmed]
PHST- 2005/09/24 09:00 [medline]
PHST- 2005/02/01 09:00 [entrez]
AID - S0167-0115(04)00424-0 [pii]
AID - 10.1016/j.regpep.2004.11.006 [doi]
PST - ppublish
SO  - Regul Pept. 2005 Apr 15;127(1-3):159-67. doi: 10.1016/j.regpep.2004.11.006.