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

Access this Article

Author(s)

    • Beei Chang BEEI Chang
    • 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
    • KUMAGAI Yoshito
    • Master's Program in environmental Sciences, Graduate School of Life and Environmental 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, 2013-10-01

    The Japanese Society of Toxicology

References:  17

Codes

  • NII Article ID (NAID)
    10031191738
  • NII NACSIS-CAT ID (NCID)
    AN00002808
  • Text Lang
    ENG
  • Article Type
    SHO
  • ISSN
    03881350
  • NDL Article ID
    024934393
  • NDL Call No.
    Z19-1022
  • Data Source
    CJP  NDL  J-STAGE 
Page Top