Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK)

Takatoshi Saito, Hiroshi Itoh, Jun Yamashita, Kentaro Doi, Tae Hwa Chun, Tokuji Tanaka, Mayumi Inoue, Ken Masatsugu, Yasutomo Fukunaga, Naoki Sawada, Satsuki Sakaguchi, Hiroshi Arai, Katsuyoshi Tojo, Naoko Tajima, Tatsuo Hosoya, Kazuwa Nakao

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 H 2O2 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 H2O 2 induced marked activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was blocked by NAC. Ang II and H2O 2 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.

Original languageEnglish (US)
Pages (from-to)159-167
Number of pages9
JournalRegulatory Peptides
Volume127
Issue number1-3
DOIs
StatePublished - Apr 15 2005

Fingerprint

Homeobox Genes
Mitogen-Activated Protein Kinases
Angiotensin II
Oxidation-Reduction
Growth
Oxidative stress
Cell growth
Oxidative Stress
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Oxidants
Chemical activation
Cardiovascular system
Cardiovascular System
Down-Regulation
Genes
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • Angiotensin II
  • Gax
  • Mitogen-activated protein kinase
  • Oxidative stress
  • Vascular smooth muscle cell

Cite this

Saito, Takatoshi ; Itoh, Hiroshi ; Yamashita, Jun ; Doi, Kentaro ; Chun, Tae Hwa ; Tanaka, Tokuji ; Inoue, Mayumi ; Masatsugu, Ken ; Fukunaga, Yasutomo ; Sawada, Naoki ; Sakaguchi, Satsuki ; Arai, Hiroshi ; Tojo, Katsuyoshi ; Tajima, Naoko ; Hosoya, Tatsuo ; Nakao, Kazuwa. / Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK). In: Regulatory Peptides. 2005 ; Vol. 127, No. 1-3. pp. 159-167.
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abstract = "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 H 2O2 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 H2O 2 induced marked activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was blocked by NAC. Ang II and H2O 2 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.",
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author = "Takatoshi Saito and Hiroshi Itoh and Jun Yamashita and Kentaro Doi and Chun, {Tae Hwa} and Tokuji Tanaka and Mayumi Inoue and Ken Masatsugu and Yasutomo Fukunaga and Naoki Sawada and Satsuki Sakaguchi and Hiroshi Arai and Katsuyoshi Tojo and Naoko Tajima and Tatsuo Hosoya and Kazuwa Nakao",
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Saito, T, Itoh, H, Yamashita, J, Doi, K, Chun, TH, Tanaka, T, Inoue, M, Masatsugu, K, Fukunaga, Y, Sawada, N, Sakaguchi, S, Arai, H, Tojo, K, Tajima, N, Hosoya, T & Nakao, K 2005, 'Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK)', Regulatory Peptides, vol. 127, no. 1-3, pp. 159-167. https://doi.org/10.1016/j.regpep.2004.11.006

Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK). / Saito, Takatoshi; Itoh, Hiroshi; Yamashita, Jun; Doi, Kentaro; Chun, Tae Hwa; Tanaka, Tokuji; Inoue, Mayumi; Masatsugu, Ken; Fukunaga, Yasutomo; Sawada, Naoki; Sakaguchi, Satsuki; Arai, Hiroshi; Tojo, Katsuyoshi; Tajima, Naoko; Hosoya, Tatsuo; Nakao, Kazuwa.

In: Regulatory Peptides, Vol. 127, No. 1-3, 15.04.2005, p. 159-167.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK)

AU - Saito, Takatoshi

AU - Itoh, Hiroshi

AU - Yamashita, Jun

AU - Doi, Kentaro

AU - Chun, Tae Hwa

AU - Tanaka, Tokuji

AU - Inoue, Mayumi

AU - Masatsugu, Ken

AU - Fukunaga, Yasutomo

AU - Sawada, Naoki

AU - Sakaguchi, Satsuki

AU - Arai, Hiroshi

AU - Tojo, Katsuyoshi

AU - Tajima, Naoko

AU - Hosoya, Tatsuo

AU - Nakao, Kazuwa

PY - 2005/4/15

Y1 - 2005/4/15

N2 - 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 H 2O2 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 H2O 2 induced marked activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was blocked by NAC. Ang II and H2O 2 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.

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 H 2O2 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 H2O 2 induced marked activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was blocked by NAC. Ang II and H2O 2 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.

KW - Angiotensin II

KW - Gax

KW - Mitogen-activated protein kinase

KW - Oxidative stress

KW - Vascular smooth muscle cell

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