{"@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/1361981470732497152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1111/j.1742-4658.2007.05735.x"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2007.05735.x"}},{"identifier":{"@type":"URI","@value":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2007.05735.x"}}],"dc:title":[{"@value":"4‐Phenylbutyrate restores the functionality of a misfolded mutant low‐density lipoprotein receptor"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Familial hypercholesterolemia is an autosomal dominant disease caused by mutations in the gene encoding the low‐density lipoprotein receptor. To date, more than 900 different mutations have been described. Transport‐defective mutations (class 2) causing partial or complete retention of the receptor in the endoplasmic reticulum are the predominant class of mutations. In a cell culture system (Chinese hamster ovary cells), we show that chemical chaperones are able to mediate rescue of a transport‐defective mutant (G544V), and that the ability to obtain rescue is mutation dependent. In particular, the low molecular mass fatty acid derivative 4‐phenylbutyrate mediated a marked increase in the transport of G544V‐mutant low‐density lipoprotein receptor to the plasma membrane. Thirty per cent of the mutant receptor was able to escape from the endoplasmic reticulum and reach the cell surface. The rescued receptor had reduced stability, but was found to be as efficient as the wild‐type low‐density lipoprotein receptor in binding and internalizing low‐density lipoprotein. In addition to 4‐phenylbutyrate, we also studied 3‐phenylpropionate and 5‐phenylvalerate, and compared their effect on rescue of the G544V‐mutant low‐density lipoprotein receptor with their ability to increase overall gene expression caused by their histone deacetylase inhibitor activity. No correlation was found. Our results indicate that the effect of these agents was not solely mediated by their ability to induce gene expression of proteins involved in intracellular transport, but rather could be due to a direct chemical chaperone activity. These data suggest that rescue of mutant low‐density lipoprotein receptor is possible and that it might be feasible to develop pharmacologic chaperones to treat familial hypercholesterolemia patients with class 2 mutations.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381981470732497157","@type":"Researcher","foaf:name":[{"@value":"Kristian Tveten"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470732497155","@type":"Researcher","foaf:name":[{"@value":"Øystein L. Holla"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470732497156","@type":"Researcher","foaf:name":[{"@value":"Trine Ranheim"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470732497154","@type":"Researcher","foaf:name":[{"@value":"Knut E. Berge"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470732497153","@type":"Researcher","foaf:name":[{"@value":"Trond P. Leren"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981470732497152","@type":"Researcher","foaf:name":[{"@value":"Mari A. Kulseth"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"1742464X"},{"@type":"EISSN","@value":"17424658"}],"prism:publicationName":[{"@value":"The FEBS Journal"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2007-03-05","prism:volume":"274","prism:number":"8","prism:startingPage":"1881","prism:endingPage":"1893"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2007.05735.x"},{"@id":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2007.05735.x"}],"createdAt":"2007-03-05","modifiedAt":"2024-02-11","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232016968704","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid"}]},{"@id":"https://cir.nii.ac.jp/crid/1360005516671650432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Indole-3-propionic acid has chemical chaperone activity and suppresses endoplasmic reticulum stress-induced neuronal cell death"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679566407808","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Discovery of Synthetic Methoxy-substituted 4-Phenylbutyric Acid Derivatives as Chemical Chaperones"},{"@value":"Discovery of synthetic methoxysubstituted - phenylbutyric acid derivatives as chemical chaperons"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679609169152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Protective Effects of 4-Phenylbutyrate Derivatives on the Neuronal Cell Death and Endoplasmic Reticulum Stress"},{"@value":"Protective effects of - phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1111/j.1742-4658.2007.05735.x"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2019.07.074_references_DOI_MJ8E0nTPD3IO864wun2Y9IFxUGt"},{"@type":"CROSSREF","@value":"10.1248/bpb.35.84_references_DOI_MJ8E0nTPD3IO864wun2Y9IFxUGt"},{"@type":"CROSSREF","@value":"10.1016/j.bmcl.2014.12.080_references_DOI_MJ8E0nTPD3IO864wun2Y9IFxUGt"},{"@type":"CROSSREF","@value":"10.1246/cl.130419_references_DOI_MJ8E0nTPD3IO864wun2Y9IFxUGt"}]}