Activation of EGFR/MEK/ERK/AP-1 signaling mediated by 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary A549 cells

• Beei Chang

  Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba

• Iwamoto Noriko

  Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Inaba Takako

  Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba

• Shinkai Yasuhiro

  Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

• Kumagai Yoshito

  Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

Abstract

1,2-Naphthoquinone (1,2-NQ) is found to be an electrophile contaminated in the atmosphere. Although we found that 1,2-NQ activates epidermal growth factor receptor (EGFR) coupled to inhibition of protein tyrosine phosphatase 1B (PTP1B) activity through covalent modification of Cys121 in human epithelial A431 cells, modulation of its downstream signal transduction pathway caused by 1,2-NQ remains to be elucidated. In the present study, we examined whether 1,2-NQ could affect such cellular signaling in human pulmonary A549 cells. Exposure of A549 cells to 1,2-NQ increased EGFR phosphorylation, resulting in activation of MEK/ERK signaling that was blocked by either PD15035 or PD98059. As a result, DNA binding activity of transcription factor AP-1 was enhanced during exposure to 1,2-NQ in the cells. These results suggest that the atmospheric electrophile phosphorylates EGFR, thereby activating the MEK/ERK/AP-1 signal transduction pathway in A549 cells.

Journal

• The Journal of Toxicological Sciences

  The Journal of Toxicological Sciences 38 (5), 793-797, 2013

  The Japanese Society of Toxicology

Keywords

• Electrophile
• Covalent modification
• Signal transduction
• EGFR

Details

• CRID: 1390282679882876416
• NII Article ID: 10031191738
• NII Book ID: AN00002808
• DOI: 10.2131/jts.38.793
• COI: 1:CAS:528:DC%2BC3sXhslyitbrL
• ISSN: 18803989
• ISSN: 03881350
• NDL BIB ID: 024934393
• PubMed: 24067727
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024934393
• Web Site: https://www.jstage.jst.go.jp/article/jts/38/5/38_793/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014183107
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed