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Blockade by SB203580 of Cyp1a1 Induction by 2,3,7,8‐Tetrachlorodibenzo‐ p ‐dioxin, and the Possible Mechanism: Possible Involvement of the p38 Mitogen‐Activated Protein Kinase Pathway in Shuttling of Ah Receptor Overexpressed in COS‐7 Cells
Author(s) -
SHIBAZAKI MASAHIKO,
TAKEUCHI TAKAHASHI,
AHMED SOHEL,
KIKUCHIA HIDEAKI
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.034
Subject(s) - aryl hydrocarbon receptor , p38 mitogen activated protein kinases , aryl hydrocarbon receptor nuclear translocator , nucleus , protein kinase a , chemistry , kinase , microbiology and biotechnology , cytoplasm , reporter gene , chromosomal translocation , mitogen activated protein kinase , signal transduction , transcription factor , gene , biology , gene expression , biochemistry
A bstract : A transiently overexpressed aryl hydrocarbon receptor (AhR) became translocated into the nucleus of COS‐7 cells without treatment with any ligand, such as 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin. This spontaneous AhR translocation into the nucleus was reduced by pretreatment of the recipient cells with the p38 mitogen‐activated protein (MAP) kinase inhibitor SB203580. Immunofluorescent microscopic analysis revealed that SB203580 treatment increased the fluorescence intensity of AhR within the cytoplasm. An analogue compound, SB202474, which does not inhibit p38 MAP kinase, did not reduce AhR translocation into the nucleus. Moreover, a reporter gene assay showed that the AhR spontaneously translocated into the nucleus activated reporter gene transcription and that SB203580 suppressed its transcriptional activity. From these data we conclude that the p38 MAP kinase pathway is involved in determining AhR cellular localization in COS‐7 cells overexpressing AhR.