Activation of EGFR/MEK/ERK/AP-1 signaling mediated by 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary A549 cells
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- Beei Chang
- Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba
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- Iwamoto Noriko
- Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
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- Inaba Takako
- Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba
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- 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
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- 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
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抄録
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.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 38 (5), 793-797, 2013
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679882876416
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- NII論文ID
- 10031191738
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3sXhslyitbrL
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024934393
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- PubMed
- 24067727
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可