{"created":"2023-07-27T06:28:35.995285+00:00","id":13192,"links":{},"metadata":{"_buckets":{"deposit":"daec3e89-d710-4b15-961b-47b053b1e5be"},"_deposit":{"created_by":3,"id":"13192","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"13192"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00013192","sets":["1132:1133:1134"]},"author_link":["21115","21120","20107","21124","21116","21121","21119","20266","21123","21118","21122","389","21117"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1981-01-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"5","bibliographicPageEnd":"1540","bibliographicPageStart":"1532","bibliographicVolumeNumber":"67","bibliographic_titles":[{"bibliographic_title":"Journal of Clinical Investigation"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of 125I-LDL were 0.5 ± 0.3 ng/mg protein (mean ± SEM), 14 ± 8 and 8 ± 6 ng/mg protein per 6 h (four normal cells; 44 ± 3, 386 ± 32, and 1,335 ± 214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of 12:5I-LDL were 6 ± 2, 29 ± 8, and 90 ± 32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed ~46% of the normal activities of receptor. ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [14C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 μg/ml. However, at 0.05 μg/ml of ML-236 B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 μg/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and heterozygote, sterol synthesis was inhibited even after preincubation. These results suggest that (a) the inhibitory effect of ML-236B is overcome in homozygote cells by their high intracellular levels of HMG-CoA reductase and (b) that a higher dose of ML-236B may be required to lower serum cholesterol levels in FH homozygotes than in heterozygotes.","subitem_description_type":"Abstract"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学大学院医学系研究科　","subitem_description_type":"Other"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Clinical Investigation"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1172/jci110184","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA00695520","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0021-9738","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Haba, Toshihiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mabuchi, Hiroshi"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Yoshimura, Akira"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Watanabe, Akira"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wakasugi, Takanobu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tatami, Ryozo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ueda, Kosei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ueda, Ryosei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kametani, Tomio"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Koizumi, Junji"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Miyamoto, Susumu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takeda, Ryoyu"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Takeshita, Haruo"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-03"}],"displaytype":"detail","filename":"ME-PR-MABUCHI-H-1532.pdf","filesize":[{"value":"661.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ME-PR-MABUCHI-H-1532.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/13192/files/ME-PR-MABUCHI-H-1532.pdf"},"version_id":"52882081-6e84-4639-aa08-ab0e3f73f2bb"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia"}]},"item_type_id":"4","owner":"3","path":["1134"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-03"},"publish_date":"2017-10-03","publish_status":"0","recid":"13192","relation_version_is_last":true,"title":["Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-07-27T12:30:56.886252+00:00"}