{"@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/1360021390564602112.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/nu15081904"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/2072-6643/15/8/1904/pdf"}},{"identifier":{"@type":"PMID","@value":"37111122"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Vegetable Oil-Peroxidation Product ‘Hydroxynonenal’ Causes Hepatocyte Injury and Steatosis via Hsp70.1 and BHMT Disorders in the Monkey Liver"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Hsp70.1 has a dual function as a chaperone protein and lysosomal stabilizer. In 2009, we reported that calpain-mediated cleavage of carbonylated Hsp70.1 causes neuronal death by inducing lysosomal rupture in the hippocampal CA1 neurons of monkeys after transient brain ischemia. Recently, we also reported that consecutive injections of the vegetable oil-peroxidation product ‘hydroxynonenal’ induce hepatocyte death via a similar cascade in monkeys. As Hsp70.1 is also related to fatty acid β-oxidation in the liver, its deficiency causes fat accumulation. The genetic deletion of betaine-homocysteine S-methyltransferase (BHMT) was reported to perturb choline metabolism, inducing a decrease in phosphatidylcholine and resulting in hepatic steatosis. Here, focusing on Hsp70.1 and BHMT disorders, we studied the mechanisms of hepatocyte degeneration and steatosis. Monkey liver tissues with and without hydroxynonenal injections were compared using proteomics, immunoblotting, immunohistochemical, and electron microscopy-based analyses. Western blotting showed that neither Hsp70.1 nor BHMT were upregulated, but an increased cleavage was observed in both. Proteomics showed a marked downregulation of Hsp70.1, albeit a two-fold increase in the carbonylated BHMT. Hsp70.1 carbonylation was negligible, in contrast to the ischemic hippocampus, which was associated with ~10-fold increments. Although histologically, the control liver showed very little lipid deposition, numerous tiny lipid droplets were seen within and around the degenerating/dying hepatocytes in monkeys after the hydroxynonenal injections. Electron microscopy showed permeabilization/rupture of lysosomal membranes, dissolution of the mitochondria and rough ER membranes, and proliferation of abnormal peroxisomes. It is probable that the disruption of the rough ER caused impaired synthesis of the Hsp70.1 and BHMT proteins, while impairment of the mitochondria and peroxisomes contributed to the sustained generation of reactive oxygen species. In addition, hydroxynonenal-induced disorders facilitated degeneration and steatosis in the hepatocytes.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420001326222326784","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"60135077"},{"@type":"NRID","@value":"1000060135077"},{"@type":"CINII_AUTHOR_ID","@value":"DA0714495X"},{"@type":"URI","@value":"https://ci.nii.ac.jp/author/DA0714495X#entity"},{"@type":"URI","@value":"https://viaf.org/viaf/NII%7CDA0714495X"},{"@type":"NRID","@value":"9000020632841"},{"@type":"NRID","@value":"9000020525152"},{"@type":"NRID","@value":"9000023112438"},{"@type":"NRID","@value":"9000347094130"},{"@type":"NRID","@value":"9000000904018"},{"@type":"NRID","@value":"9000020449157"},{"@type":"NRID","@value":"9000003613680"},{"@type":"NRID","@value":"9000020524993"},{"@type":"NRID","@value":"9000347092289"},{"@type":"NRID","@value":"9000020657446"},{"@type":"NRID","@value":"9000001950148"},{"@type":"NRID","@value":"9000001981087"},{"@type":"NRID","@value":"9000003624310"},{"@type":"NRID","@value":"9000020449743"},{"@type":"NRID","@value":"9000020420261"},{"@type":"NRID","@value":"9000020565711"},{"@type":"NRID","@value":"9000410014709"},{"@type":"NRID","@value":"9000398610128"},{"@type":"NRID","@value":"9000020545837"},{"@type":"NRID","@value":"9000022448009"},{"@type":"NRID","@value":"9000276430929"},{"@type":"NRID","@value":"9000399374235"},{"@type":"NRID","@value":"9000020392533"},{"@type":"NRID","@value":"9000000904095"},{"@type":"NRID","@value":"9000020517793"},{"@type":"NRID","@value":"9000018827467"},{"@type":"NRID","@value":"9000020547034"},{"@type":"NRID","@value":"9000020472950"},{"@type":"NRID","@value":"9000020621938"},{"@type":"NRID","@value":"9000277058942"},{"@type":"NRID","@value":"9000347091233"},{"@type":"NRID","@value":"9000003608489"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0009683"}],"foaf:name":[{"@value":"Tetsumori Yamashima"}],"jpcoar:affiliationName":[{"@value":"Department of Psychiatry and Behavioral Science, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"},{"@value":"Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"},{"@value":"Department of Cell Metabolism and Nutrition, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564602121","@type":"Researcher","foaf:name":[{"@value":"Yurie Mori"}],"jpcoar:affiliationName":[{"@value":"Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564602147","@type":"Researcher","foaf:name":[{"@value":"Takuya Seike"}],"jpcoar:affiliationName":[{"@value":"Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564602141","@type":"Researcher","foaf:name":[{"@value":"Sharif Ahmed"}],"jpcoar:affiliationName":[{"@value":"Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564602244","@type":"Researcher","foaf:name":[{"@value":"Piyakarn Boontem"}],"jpcoar:affiliationName":[{"@value":"Department of Cell Metabolism and Nutrition, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564602113","@type":"Researcher","foaf:name":[{"@value":"Shihui Li"}],"jpcoar:affiliationName":[{"@value":"Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420564276159334784","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10277006"},{"@type":"NRID","@value":"1000010277006"},{"@type":"NRID","@value":"9000003112020"},{"@type":"NRID","@value":"9000107344578"},{"@type":"NRID","@value":"9000347094132"},{"@type":"NRID","@value":"9000006775687"},{"@type":"NRID","@value":"9000317128074"},{"@type":"NRID","@value":"9000410014704"},{"@type":"NRID","@value":"9000257822647"},{"@type":"NRID","@value":"9000011245105"},{"@type":"NRID","@value":"9000403597859"},{"@type":"NRID","@value":"9000386257864"},{"@type":"NRID","@value":"9000345266637"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/TaChi-1909_SaShi1808"}],"foaf:name":[{"@value":"Shinji Oikawa"}],"jpcoar:affiliationName":[{"@value":"Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, 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Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390564601989","@type":"Researcher","foaf:name":[{"@value":"Shuichi Kaneko"}],"jpcoar:affiliationName":[{"@value":"Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326226003328","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90345611"},{"@type":"NRID","@value":"1000090345611"},{"@type":"NRID","@value":"9000024741848"},{"@type":"NRID","@value":"9000283216914"},{"@type":"NRID","@value":"9000000340987"},{"@type":"NRID","@value":"9000237899191"},{"@type":"NRID","@value":"9000023381791"},{"@type":"NRID","@value":"9000415082181"},{"@type":"NRID","@value":"9000415082193"},{"@type":"NRID","@value":"9000313204504"},{"@type":"NRID","@value":"9000406042501"},{"@type":"NRID","@value":"9000392782674"},{"@type":"NRID","@value":"9000237898872"},{"@type":"NRID","@value":"9000237897569"},{"@type":"NRID","@value":"9000259289469"},{"@type":"NRID","@value":"9000001068323"},{"@type":"NRID","@value":"9000315686792"},{"@type":"NRID","@value":"9000345215874"},{"@type":"NRID","@value":"9000023232529"},{"@type":"NRID","@value":"9000334429922"},{"@type":"NRID","@value":"9000250756097"},{"@type":"NRID","@value":"9000257186858"},{"@type":"NRID","@value":"9000021451917"},{"@type":"NRID","@value":"9000409578463"},{"@type":"NRID","@value":"9000409578449"},{"@type":"NRID","@value":"9000412412641"},{"@type":"NRID","@value":"9000023579779"},{"@type":"NRID","@value":"9000237912743"},{"@type":"NRID","@value":"9000412587837"},{"@type":"NRID","@value":"9000283216997"},{"@type":"NRID","@value":"9000263044165"},{"@type":"NRID","@value":"9000237898624"},{"@type":"NRID","@value":"9000327105699"},{"@type":"NRID","@value":"9000401431781"},{"@type":"NRID","@value":"9000023586543"},{"@type":"NRID","@value":"9000265248634"},{"@type":"NRID","@value":"9000278500306"},{"@type":"NRID","@value":"9000274304270"},{"@type":"NRID","@value":"9000242351281"},{"@type":"NRID","@value":"9000313204513"},{"@type":"NRID","@value":"9000339142580"},{"@type":"NRID","@value":"9000291889814"},{"@type":"NRID","@value":"9000402798867"},{"@type":"NRID","@value":"9000237898684"},{"@type":"NRID","@value":"9000024726738"},{"@type":"NRID","@value":"9000256344240"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0200921"}],"foaf:name":[{"@value":"Eishiro Mizukoshi"}],"jpcoar:affiliationName":[{"@value":"Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20726643"}],"prism:publicationName":[{"@value":"Nutrients"}],"dc:publisher":[{"@value":"MDPI AG"}],"prism:publicationDate":"2023-04-14","prism:volume":"15","prism:number":"8","prism:startingPage":"1904"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://www.mdpi.com/2072-6643/15/8/1904/pdf"}],"createdAt":"2023-04-14","modifiedAt":"2025-10-10","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Fatty%20Liver","dc:title":"Fatty Liver"},{"@id":"https://cir.nii.ac.jp/all?q=Betaine-Homocysteine%20S-Methyltransferase","dc:title":"Betaine-Homocysteine S-Methyltransferase"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Death","dc:title":"Cell Death"},{"@id":"https://cir.nii.ac.jp/all?q=Liver","dc:title":"Liver"},{"@id":"https://cir.nii.ac.jp/all?q=Ischemia","dc:title":"Ischemia"},{"@id":"https://cir.nii.ac.jp/all?q=Hepatocytes","dc:title":"Hepatocytes"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=betaine-homocysteine%20%3Ci%3ES%3C/i%3E-methyltransferase;%20%3Ci%3Ecalpain-cathepsin%20hypothesis%3C/i%3E;%20carbonylation;%20cell%20death;%20lysosomal%20rupture;%20phosphatidylcholine","dc:title":"betaine-homocysteine <i>S</i>-methyltransferase; <i>calpain-cathepsin hypothesis</i>; carbonylation; cell death; lysosomal rupture; phosphatidylcholine"},{"@id":"https://cir.nii.ac.jp/all?q=Haplorhini","dc:title":"Haplorhini"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782014951680","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"19H04029"},{"@type":"JGN","@value":"JP19H04029"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19H04029/"}],"notation":[{"@language":"ja","@value":"食用油に由来するヒドロキシノネナールが生活習慣病を惹起する機序"},{"@language":"en","@value":"Cooking oil-derived hydroxynonenal and lifestyle-related diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1040018351904415104","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"23K27526"},{"@type":"JGN","@value":"JP23K27526"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23K27526/"}],"notation":[{"@language":"ja","@value":"診断閾下を含む自閉スペクトラム症の生物学的検討"},{"@language":"en","@value":"Biological investigation of autism spectrum disorder including diagnostic thresholds."}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256991599616","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"19H03885"},{"@type":"JGN","@value":"JP19H03885"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19H03885/"}],"notation":[{"@language":"ja","@value":"認知症における血中エクソソーム内包酸化損傷タンパク質の変動解析とリスク診断"},{"@language":"en","@value":"Analysis of oxidatively damaged proteins in blood including exosomes in dementia and risk assessment for dementia"}]},{"@id":"https://cir.nii.ac.jp/crid/1040287907231056000","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"21H02899"},{"@type":"JGN","@value":"JP21H02899"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21H02899/"}],"notation":[{"@language":"ja","@value":"肝細胞がんにおける多細胞間相互作用の解明による新規がん免疫療法開発の基盤研究"},{"@language":"en","@value":"Fundamental research for the development of novel cancer immunotherapy by elucidating multicellular interactions in hepatocellular carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1040299826881261824","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"23K27838"},{"@type":"JGN","@value":"JP23K27838"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23K27838/"}],"notation":[{"@language":"ja","@value":"若年性アルツハイマー病の原因解明と早期血液バイオマーカーの探索"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050565162620080128","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"Protocols for Enzymatic Fluorometric Assays to Quantify Phospholipid Classes."}]},{"@id":"https://cir.nii.ac.jp/crid/1360011143935899520","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Stat3 controls lysosomal-mediated cell death in 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human fatty and nonfatty NASH"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302870455246720","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Nonalcoholic fatty liver disease in the pediatric population: a review"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302870455259008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The peroxisome: a new cytoplasmic organelle"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094077243136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"4-Hydroxynonenal, a Product of Lipid Peroxidation, Damages Cholinergic Neurons and Impairs Visuospatial Memory in Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094915285760","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"S-adenosylmethionine metabolism and liver 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