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Suppression of P-glycoprotein by cigarette smoke extract in human lung-derived A549/P-gp cells.
Takano, Mikihisa; Higa, Shuhei; Furuichi, Yuma; Naka, Ryosuke; Yumoto, Ryoko.
Afiliación
  • Takano M; Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan. Electronic address: takanom@hiroshima-u.ac.jp.
  • Higa S; Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
  • Furuichi Y; Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
  • Naka R; Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
  • Yumoto R; Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Drug Metab Pharmacokinet ; 35(2): 214-219, 2020 Apr.
Article en En | MEDLINE | ID: mdl-32037157
Effect of long-term treatment with cigarette smoke extract (CSE) on the function and expression of P-glycoprotein (P-gp) in lung alveolar epithelial cells was examined using A549/P-gp cell line expressing P-gp. CSE treatment suppressed P-gp activity in a concentration- and treatment time-dependent manner. The suppression of P-gp activity by CSE was irreversible for at least 96 h after removal of CSE. In addition, CSE treatment suppressed the expression of P-gp mRNA and protein. In order to understand the mechanisms underlying P-gp suppression by CSE, the role of reactive oxygen species (ROS) was examined. CSE treatment increased intracellular ROS level, and suppressed catalase activity. α-Tocopherol suppressed ROS production by CSE, and ameliorated the suppression of P-gp activity by CSE, suggesting that ROS is involved in CSE-induced suppression of P-gp. The role of intracellular signaling pathways such as the nuclear factor κB and mitogen-activated protein kinase pathways was also examined. Among these pathways, the involvement of extracellular signal-regulated kinase (ERK) pathway was suggested. Taken together, long-term CSE treatment may suppress P-gp via modulation of ROS level and ERK pathway in alveolar epithelial cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Humo / Extractos Vegetales / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Humo / Extractos Vegetales / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido