{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360283691780417536.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/ncomms4334"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/ncomms4334.pdf"}},{"identifier":{"@type":"URI","@value":"http://www.nature.com/articles/ncomms4334"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/ncomms4334.pdf"}},{"identifier":{"@type":"PMID","@value":"24566390"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Histamine H3 receptors aggravate cerebral ischaemic injury by histamine-independent mechanisms"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion (I/R) injury remains unknown. Here we show that H3R expression is upregulated after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R antagonists, a histidine decarboxylase (HDC) inhibitor and HDC knockout all fail to compromise the protection by H3R blockade. H3R blockade inhibits mTOR phosphorylation and reinforces autophagy. The neuroprotection by H3R antagonism is reversed by 3-methyladenine and siRNA for<jats:italic>Atg7</jats:italic>, and is diminished in<jats:italic>Atg5</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup>mouse embryonic fibroblasts. Furthermore, the peptide Tat-H3R<jats:sub>CT414-436</jats:sub>, which blocks CLIC4 binding with H3Rs, or siRNA for<jats:italic>CLIC4</jats:italic>, further increases I/R-induced autophagy and protects against I/R injury. Therefore, H3R promotes I/R injury while its antagonism protects against ischaemic injury via histamine-independent mechanisms that involve suppressing H3R/CLIC4 binding-activated autophagy, suggesting that H3R inhibition is a therapeutic target for cerebral ischaemia.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380284919970235273","@type":"Researcher","foaf:name":[{"@value":"Haijing Yan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235268","@type":"Researcher","foaf:name":[{"@value":"Xiangnan Zhang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235265","@type":"Researcher","foaf:name":[{"@value":"Weiwei Hu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235271","@type":"Researcher","foaf:name":[{"@value":"Jing Ma"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235272","@type":"Researcher","foaf:name":[{"@value":"Weiwei Hou"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235264","@type":"Researcher","foaf:name":[{"@value":"Xingzhou Zhang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235274","@type":"Researcher","foaf:name":[{"@value":"Xiaofen Wang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235275","@type":"Researcher","foaf:name":[{"@value":"Jieqiong Gao"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235267","@type":"Researcher","foaf:name":[{"@value":"Yao Shen"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235269","@type":"Researcher","foaf:name":[{"@value":"Jianxin Lv"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235276","@type":"Researcher","foaf:name":[{"@value":"Hiroshi Ohtsu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235277","@type":"Researcher","foaf:name":[{"@value":"Feng Han"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235270","@type":"Researcher","foaf:name":[{"@value":"Guanghui Wang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380284919970235266","@type":"Researcher","foaf:name":[{"@value":"Zhong Chen"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20411723"}],"prism:publicationName":[{"@value":"Nature Communications"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2014-02-25","prism:volume":"5","prism:number":"1"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["http://creativecommons.org/licenses/by/3.0"],"url":[{"@id":"http://www.nature.com/articles/ncomms4334.pdf"},{"@id":"http://www.nature.com/articles/ncomms4334"},{"@id":"https://www.nature.com/articles/ncomms4334.pdf"}],"createdAt":"2014-02-25","modifiedAt":"2024-05-24","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Histidine%20Decarboxylase","dc:title":"Histidine Decarboxylase"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"},{"@id":"https://cir.nii.ac.jp/all?q=Autophagy-Related%20Protein%205","dc:title":"Autophagy-Related Protein 5"},{"@id":"https://cir.nii.ac.jp/all?q=Brain%20Ischemia","dc:title":"Brain Ischemia"},{"@id":"https://cir.nii.ac.jp/all?q=Histamine%20Agonists","dc:title":"Histamine Agonists"},{"@id":"https://cir.nii.ac.jp/all?q=Mitochondrial%20Proteins","dc:title":"Mitochondrial Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Chloride%20Channels","dc:title":"Chloride Channels"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Histamine%20H3","dc:title":"Receptors, Histamine H3"},{"@id":"https://cir.nii.ac.jp/all?q=Microtubule-Associated%20Proteins","dc:title":"Microtubule-Associated Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Histamine","dc:title":"Histamine"},{"@id":"https://cir.nii.ac.jp/all?q=Histamine%20H3%20Antagonists","dc:title":"Histamine H3 Antagonists"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782301805056","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"26460332"},{"@type":"JGN","@value":"JP26460332"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26460332/"}],"notation":[{"@language":"ja","@value":"トランスジェニックマウスを使ったヒスタミン産生細胞の病態解析"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011143993048448","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Roles of Autophagy in Cerebral Ischemia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145281627392","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The effects of histamine H3-receptor antagonists on amygdaloid kindled seizures in 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