Mechanism of oxidative stress-induced GADD153 gene expression in vascular smooth muscle cells.
Oxidative stress plays a critical role in normal functioning of cardiac and vascular cells as well as in the pathogenesis of cardiovascular disease. Growth arrest and DNA damage-inducible gene 153 (GADD153), which is upregulated by oxidative stress, regulates the cell cycle and apoptosis. Previously an AP-1 was reported to contribute significantly to GADD153 gene transcriptional activation by oxidative stress. Recently, we have reported that GADD153 gene promoter activity is negatively regulated by nuclear factor 1 (NF1), in vascular smooth muscle cells (VSMCs). The aim of this study was to elucidate the roles of AP-1 and NF1 in GADD153 gene induction by oxidative stress in VSMCs. H(2)O(2) induced GADD153 mRNA and reduced NF1 mRNA expression. In the electromobility shift assay, H(2)O(2) induced AP-1-binding activity and reduced NF1-binding activity. Overexpression of NF1 significantly suppressed the induction of the GADD153 gene after treatment with H(2)O(2). These results revealed that induction of the GADD153 gene by oxidative stress is regulated mainly by two nuclear factors, NF1 and AP-1.
Tang
Jia-Rong
JR
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, 791-0295, Japan.
Nakamura
Michitsugu
M
Okura
Takafumi
T
Takata
Yasunori
Y
Watanabe
Sanae
S
Yang
Zhao-Hui
ZH
Liu
Jun
J
Kitami
Yutaka
Y
Hiwada
Kunio
K
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics*; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D051742:Transcription Factor CHOP; D006861:Hydrogen Peroxide