{"@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/1360021391871654144.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.redox.2023.102876"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S221323172300277X?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S221323172300277X?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"37703666"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Glucuronic acid is a novel source of pentosidine, associated with schizophrenia"}],"description":[{"notation":[{"@value":"Pentosidine (PEN) is an advanced glycation end-product (AGEs), where a fluorescent cross-link is formed between lysine and arginine residues in proteins. Accumulation of PEN is associated with aging and various diseases. We previously reported that a subpopulation of patients with schizophrenia showed PEN accumulation in the blood, having severe clinical features. PEN is thought to be produced from glucose, fructose, pentoses, or ascorbate. However, patients with schizophrenia with high PEN levels present no elevation of these precursors of PEN in their blood. Therefore, the molecular mechanisms underlying PEN accumulation and the molecular pathogenesis of schizophrenia associated with PEN accumulation remain unclear. Here, we identified glucuronic acid (GlcA) as a novel precursor of PEN from the plasma of subjects with high PEN levels. We demonstrated that PEN can be generated from GlcA, both in vitro and in vivo. Furthermore, we found that GlcA was associated with the diagnosis of schizophrenia. Among patients with high PEN, the proportion of those who also have high GlcA is 25.6%. We also showed that Aldo-keto reductase (AKR) activity to degrade GlcA was decreased in patients with schizophrenia, and its activity was negatively correlated with GlcA levels in the plasma. This is the first report to show that PEN is generated from GlcA. In the future, this finding will contribute to understanding the molecular pathogenesis of not only schizophrenia but also other diseases with PEN accumulation."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276182006272","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10549421"},{"@type":"NRID","@value":"1000010549421"},{"@type":"NRID","@value":"9000412602218"},{"@type":"NRID","@value":"9000019147019"},{"@type":"NRID","@value":"9000002742784"},{"@type":"NRID","@value":"9000367420719"},{"@type":"NRID","@value":"9000391519892"},{"@type":"NRID","@value":"9000010529751"},{"@type":"NRID","@value":"9000345376645"},{"@type":"NRID","@value":"9000408449188"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/toriumi1207"}],"foaf:name":[{"@value":"Kazuya Toriumi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654166","@type":"Researcher","foaf:name":[{"@value":"Kyoka Iino"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654027","@type":"Researcher","foaf:name":[{"@value":"Azuna Ozawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654157","@type":"Researcher","foaf:name":[{"@value":"Mitsuhiro Miyashita"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654025","@type":"Researcher","foaf:name":[{"@value":"Syudo Yamasaki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654028","@type":"Researcher","foaf:name":[{"@value":"Kazuhiro Suzuki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654150","@type":"Researcher","foaf:name":[{"@value":"Hikari Sugawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654283","@type":"Researcher","foaf:name":[{"@value":"Koichi Tabata"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654149","@type":"Researcher","foaf:name":[{"@value":"Satoshi Yamaguchi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654018","@type":"Researcher","foaf:name":[{"@value":"Satoshi Usami"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654188","@type":"Researcher","foaf:name":[{"@value":"Masanari Itokawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654024","@type":"Researcher","foaf:name":[{"@value":"Atsushi Nishida"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654020","@type":"Researcher","foaf:name":[{"@value":"Ryoji Nagai"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654160","@type":"Researcher","foaf:name":[{"@value":"Hidenori Kamiguchi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391871654281","@type":"Researcher","foaf:name":[{"@value":"Makoto Arai"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"22132317"}],"prism:publicationName":[{"@value":"Redox Biology"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2023-11","prism:volume":"67","prism:startingPage":"102876"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","http://creativecommons.org/licenses/by-nc-nd/4.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S221323172300277X?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S221323172300277X?httpAccept=text/plain"}],"createdAt":"2023-09-09","modifiedAt":"2025-11-01","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Glycation%20End%20Products,%20Advanced","dc:title":"Glycation End Products, Advanced"},{"@id":"https://cir.nii.ac.jp/all?q=Medicine%20(General)","dc:title":"Medicine (General)"},{"@id":"https://cir.nii.ac.jp/all?q=Pentosidine","dc:title":"Pentosidine"},{"@id":"https://cir.nii.ac.jp/all?q=QH301-705.5","dc:title":"QH301-705.5"},{"@id":"https://cir.nii.ac.jp/all?q=Aldo-keto%20reductase","dc:title":"Aldo-keto reductase"},{"@id":"https://cir.nii.ac.jp/all?q=Lysine","dc:title":"Lysine"},{"@id":"https://cir.nii.ac.jp/all?q=Arginine","dc:title":"Arginine"},{"@id":"https://cir.nii.ac.jp/all?q=Glucuronic%20acid","dc:title":"Glucuronic acid"},{"@id":"https://cir.nii.ac.jp/all?q=R5-920","dc:title":"R5-920"},{"@id":"https://cir.nii.ac.jp/all?q=Glucuronic%20Acid","dc:title":"Glucuronic Acid"},{"@id":"https://cir.nii.ac.jp/all?q=Schizophrenia","dc:title":"Schizophrenia"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Advanced%20glycation%20end-products","dc:title":"Advanced glycation end-products"},{"@id":"https://cir.nii.ac.jp/all?q=Biology%20(General)","dc:title":"Biology (General)"},{"@id":"https://cir.nii.ac.jp/all?q=Research%20Paper","dc:title":"Research Paper"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040573407543035392","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22K07609"},{"@type":"JGN","@value":"JP22K07609"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K07609/"}],"notation":[{"@language":"ja","@value":"新規ペントシジン産生経路に基づく統合失調症分子病態の解明"},{"@language":"en","@value":"Elucidation of the molecular pathogenesis of schizophrenia based on a novel pentosidine-producing pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1040581301857839744","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"23K27535"},{"@type":"JGN","@value":"JP23K27535"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23K27535/"}],"notation":[{"@language":"ja","@value":"糖化トラジェクトリー制御を標的とする統合失調症の分子病態解明と操作"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360005519082833920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Identification of a novel advanced glycation end product derived from lactaldehyde"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145250574464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Metabolic Footprint of Diabetes: A Multiplatform Metabolomics Study in an Epidemiological 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The Dialong study"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302871113836288","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Protein Modification with Ribose Generates Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302871327009792","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302871505412224","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Kinetics of Nonenzymatic Glycation of Ribonuclease A Leading to Advanced Glycation End Products. Paradoxical Inhibition by Ribose Leads to Facile Isolation of Protein Intermediate for Rapid Post-Amadori Studies"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302871506219008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits"}]},{"@id":"https://cir.nii.ac.jp/crid/1360306504593809024","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism."}]},{"@id":"https://cir.nii.ac.jp/crid/1360567182404004480","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567184712681216","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Clinical Features of Schizophrenia With Enhanced Carbonyl Stress"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095091536256","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence."}]},{"@id":"https://cir.nii.ac.jp/crid/1360576121554796032","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Protein glycation – biomarkers of metabolic dysfunction and early-stage decline in health in the era of precision medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1360580237581146112","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Glucuronic acid and the ethanol metabolite ethyl-glucuronide cause toll-like receptor 4 activation and enhanced pain"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848656925041792","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"In vivo role of aldehyde reductase"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569302067584","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"2-Ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine) Is a Newly Identified Advanced Glycation End Product in Cataractous and Aged Human Lenses"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570310361600","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593693327616","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Advanced glycation end products and cognitive impairment in schizophrenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593693459072","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820396628992","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Glycosylation of lysine-containing pentapeptides by glucuronic acid: new insights into the Maillard reaction"}]},{"@id":"https://cir.nii.ac.jp/crid/1360868145898833152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content."}]},{"@id":"https://cir.nii.ac.jp/crid/1360869854341960960","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of pentosidine accumulation in stress-induced social behavioral deficits"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137043477777920","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The aldo-keto reductases (AKRs): Overview"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137043529184128","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Carbonyl Stress and Microinflammation-Related Molecules as Potential Biomarkers in Schizophrenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137043760718208","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanism of formation of the Maillard protein cross-link pentosidine. 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