{"created":"2025-02-19T01:15:30.832930+00:00","id":2012632,"links":{},"metadata":{"_buckets":{"deposit":"7be1e9a6-36ad-436e-a76c-1d0978bc77c0"},"_deposit":{"created_by":51,"id":"2012632","owner":"51","owners":[51],"pid":{"revision_id":0,"type":"depid","value":"2012632"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02012632","sets":["1713853213384:1713853295607"]},"author_link":["25","1265","1536","1143"],"control_number":"2012632","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"Signaling Pathway of Histamine-induced H1R Up-regulation","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2011-07-05","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"35","bibliographicPageEnd":"30551","bibliographicPageStart":"30542","bibliographicVolumeNumber":"286","bibliographic_titles":[{"bibliographic_title":"Journal of Biological Chemistry","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKCδ-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca2+-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKCδ phosphorylation at Tyr311 and Thr505. Activation of PKCδ by H2O2 resulted in H1R mRNA up-regulation. Overexpression of PKCδ enhanced up-regulation of H1R gene expression, and knockdown of the PKCδ gene suppressed this up-regulation. Histamine or PMA caused translocation PKCδ from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKCδ/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Biochemistry and Molecular Biology","subitem_publisher_language":"en"},{"subitem_publisher":"Elsevier","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"This is an Open Access article under the CC BY license.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"1083351X","subitem_source_identifier_type":"EISSN"},{"subitem_source_identifier":"00219258","subitem_source_identifier_type":"PISSN"},{"subitem_source_identifier":"AA1202441X","subitem_source_identifier_type":"NCID"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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