{"@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/1360285706201023232.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1007/s00395-017-0621-6"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/article/10.1007/s00395-017-0621-6/fulltext.html"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/content/pdf/10.1007/s00395-017-0621-6.pdf"}},{"identifier":{"@type":"PMID","@value":"28421341"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Insufficient activation of Akt upon reperfusion because of its novel modification by reduced PP2A-B55α contributes to enlargement of infarct size by chronic kidney disease"}],"description":[{"notation":[{"@value":"Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56.3 ± 4.6 vs. 41.4 ± 2.0%). In SNx group, myocardial p-Akt-Thr308 level at baseline was elevated, and reperfusion-induced phosphorylation of p-Akt-Ser473, p-p70s6K and p-GSK-3β was significantly suppressed. Inhibition of Akt-Ser473 phosphorylation upon reperfusion by Ku-0063794 significantly increased infarct size in the Sham group but not in the SNx group. There was no difference between the two groups in activities of mTORC2 and PDK1 and protein level of PTEN. However, the PP2A regulatory subunit B55α, which specifically targets Akt-Thr308, was reduced by 24% in the SNx group. Knockdown of B55α by siRNA increased baseline p-Akt-Thr308 and blunted Akt-Ser473 phosphorylation in response to insulin-like growth factor-1 (IGF-1) in H9c2 cells. A blunted response of Akt-Ser473 to IGF-1 was also observed in HEK293 cells transfected with a p-Thr308-mimetic Akt mutant (T308D). These results indicate that increased Akt-Thr308 phosphorylation by down-regulation of B55α inhibits Akt-Ser473 phosphorylation upon reperfusion in CKD and that the impaired Akt activation by insufficient Ser473 phosphorylation upon reperfusion contributes to infarct size enlargement by CKD."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380285706201023239","@type":"Researcher","foaf:name":[{"@value":"Toshiyuki Tobisawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326220586880","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40444913"},{"@type":"NRID","@value":"1000040444913"},{"@type":"NRID","@value":"9000413890465"},{"@type":"NRID","@value":"9000014709883"},{"@type":"NRID","@value":"9000403979646"},{"@type":"NRID","@value":"9000006863839"},{"@type":"NRID","@value":"9000414514109"},{"@type":"NRID","@value":"9000398259990"},{"@type":"NRID","@value":"9000003869386"},{"@type":"NRID","@value":"9000414928037"},{"@type":"NRID","@value":"9000414812894"},{"@type":"NRID","@value":"9000415051915"}],"foaf:name":[{"@value":"Toshiyuki Yano"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023879","@type":"Researcher","foaf:name":[{"@value":"Masaya Tanno"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023491","@type":"Researcher","foaf:name":[{"@value":"Takayuki Miki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023370","@type":"Researcher","foaf:name":[{"@value":"Atsushi Kuno"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023242","@type":"Researcher","foaf:name":[{"@value":"Yukishige Kimura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023878","@type":"Researcher","foaf:name":[{"@value":"Satoko Ishikawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023364","@type":"Researcher","foaf:name":[{"@value":"Hidemichi Kouzu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023872","@type":"Researcher","foaf:name":[{"@value":"Keitaro Nishizawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380285706201023235","@type":"Researcher","foaf:name":[{"@value":"Hideaki Yoshida"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326236816256","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90199951"},{"@type":"NRID","@value":"1000090199951"},{"@type":"NRID","@value":"9000004302505"},{"@type":"NRID","@value":"9000003884858"},{"@type":"NRID","@value":"9000253225714"},{"@type":"NRID","@value":"9000024397366"},{"@type":"NRID","@value":"9000402897077"},{"@type":"NRID","@value":"9000403402864"},{"@type":"NRID","@value":"9000257777372"},{"@type":"NRID","@value":"9000257777228"},{"@type":"NRID","@value":"9000283415589"},{"@type":"NRID","@value":"9000399596780"},{"@type":"NRID","@value":"9000370746889"},{"@type":"NRID","@value":"9000242072116"},{"@type":"NRID","@value":"9000413890468"},{"@type":"NRID","@value":"9000399372043"},{"@type":"NRID","@value":"9000024406384"},{"@type":"NRID","@value":"9000021662139"},{"@type":"NRID","@value":"9000384335702"},{"@type":"NRID","@value":"9000399234144"},{"@type":"NRID","@value":"9000023099497"},{"@type":"NRID","@value":"9000022062985"},{"@type":"NRID","@value":"9000390886461"},{"@type":"NRID","@value":"9000253110304"},{"@type":"NRID","@value":"9000007156202"},{"@type":"NRID","@value":"9000414931657"},{"@type":"NRID","@value":"9000413551012"},{"@type":"NRID","@value":"9000021406370"},{"@type":"NRID","@value":"9000021328734"},{"@type":"NRID","@value":"9000403979643"},{"@type":"NRID","@value":"9000017040821"},{"@type":"NRID","@value":"9000023122634"},{"@type":"NRID","@value":"9000018183367"},{"@type":"NRID","@value":"9000300215767"},{"@type":"NRID","@value":"9000410737790"},{"@type":"NRID","@value":"9000258207102"},{"@type":"NRID","@value":"9000256875684"},{"@type":"NRID","@value":"9000009512274"},{"@type":"NRID","@value":"9000021233870"},{"@type":"NRID","@value":"9000021192490"},{"@type":"NRID","@value":"9000021161243"},{"@type":"NRID","@value":"9000021662819"},{"@type":"NRID","@value":"9000021639129"},{"@type":"NRID","@value":"9000398259995"},{"@type":"NRID","@value":"9000310330782"},{"@type":"NRID","@value":"9000252823175"},{"@type":"NRID","@value":"9000414928036"},{"@type":"NRID","@value":"9000392142731"},{"@type":"NRID","@value":"9000009610589"},{"@type":"NRID","@value":"9000018980636"},{"@type":"NRID","@value":"9000329422088"},{"@type":"NRID","@value":"9000017040496"},{"@type":"NRID","@value":"9000024397357"},{"@type":"NRID","@value":"9000319550312"},{"@type":"NRID","@value":"9000414812895"},{"@type":"NRID","@value":"9000018206038"},{"@type":"NRID","@value":"9000024474974"},{"@type":"NRID","@value":"9000022156241"},{"@type":"NRID","@value":"9000414828345"},{"@type":"NRID","@value":"9000258083814"},{"@type":"NRID","@value":"9000398169823"},{"@type":"NRID","@value":"9000410875758"},{"@type":"NRID","@value":"9000411567559"},{"@type":"NRID","@value":"9000018449164"},{"@type":"NRID","@value":"9000253110456"},{"@type":"NRID","@value":"9000256873608"},{"@type":"NRID","@value":"9000238238360"},{"@type":"NRID","@value":"9000003937399"},{"@type":"NRID","@value":"9000021414338"},{"@type":"NRID","@value":"9000369341739"},{"@type":"NRID","@value":"9000252929699"},{"@type":"NRID","@value":"9000404512277"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0019698"}],"foaf:name":[{"@value":"Tetsuji Miura"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03008428"},{"@type":"EISSN","@value":"14351803"}],"prism:publicationName":[{"@value":"Basic Research in Cardiology"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2017-04-18","prism:volume":"112","prism:number":"3","prism:startingPage":"31"},"reviewed":"false","dc:rights":["http://www.springer.com/tdm"],"url":[{"@id":"http://link.springer.com/article/10.1007/s00395-017-0621-6/fulltext.html"},{"@id":"http://link.springer.com/content/pdf/10.1007/s00395-017-0621-6.pdf"}],"createdAt":"2017-04-18","modifiedAt":"2019-09-21","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Immunoblotting","dc:title":"Immunoblotting"},{"@id":"https://cir.nii.ac.jp/all?q=Myocardial%20Infarction","dc:title":"Myocardial Infarction"},{"@id":"https://cir.nii.ac.jp/all?q=Isolated%20Heart%20Preparation","dc:title":"Isolated Heart Preparation"},{"@id":"https://cir.nii.ac.jp/all?q=Myocardial%20Reperfusion%20Injury","dc:title":"Myocardial Reperfusion Injury"},{"@id":"https://cir.nii.ac.jp/all?q=Transfection","dc:title":"Transfection"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Rats","dc:title":"Rats"},{"@id":"https://cir.nii.ac.jp/all?q=Enzyme%20Activation","dc:title":"Enzyme Activation"},{"@id":"https://cir.nii.ac.jp/all?q=Rats,%20Sprague-Dawley","dc:title":"Rats, Sprague-Dawley"},{"@id":"https://cir.nii.ac.jp/all?q=HEK293%20Cells","dc:title":"HEK293 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Knockdown%20Techniques","dc:title":"Gene Knockdown Techniques"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Immunoprecipitation","dc:title":"Immunoprecipitation"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Phosphatase%202","dc:title":"Protein Phosphatase 2"},{"@id":"https://cir.nii.ac.jp/all?q=Renal%20Insufficiency,%20Chronic","dc:title":"Renal Insufficiency, Chronic"},{"@id":"https://cir.nii.ac.jp/all?q=Proto-Oncogene%20Proteins%20c-akt","dc:title":"Proto-Oncogene Proteins c-akt"},{"@id":"https://cir.nii.ac.jp/all?q=Signal%20Transduction","dc:title":"Signal Transduction"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256891908608","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16K09505"},{"@type":"JGN","@value":"JP16K09505"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K09505/"}],"notation":[{"@language":"ja","@value":"mTORシグナル異常制御による心不全治療の開発"},{"@language":"en","@value":"The role of aberrant mTOR activation in heart failure"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282257279909376","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"26461133"},{"@type":"JGN","@value":"JP26461133"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26461133/"}],"notation":[{"@language":"ja","@value":"心筋細胞のネクロプトーシスにおけるミトコンドリア透過性遷移の役割"},{"@language":"en","@value":"Role of mitochondrial permeability transition in necroptosis of the cardiomyocyte"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004236436401664","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chronic Treatment With an Erythropoietin Receptor Ligand Prevents Chronic Kidney Disease–Induced Enlargement of Myocardial Infarct Size"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004236696230272","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Does p53 Inhibition Suppress Myocardial Ischemia–Reperfusion Injury?"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144539373312","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Does Inhibition of Glycogen Synthase Kinase Protect in Mice?"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011146280923136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Localization of mTORC2 activity inside 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ligation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093915360640","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Outcomes in CKD: What We Know and What We Need to Know"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095263978880","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cellular apoptosis in the cardiorenal axis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096146094080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Akt/PKB: one kinase, many modifications"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846642467244032","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The mPTP and its regulatory proteins: final common targets of signalling pathways for protection against necrosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846643661343104","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hypertensive Hypertrophied Myocardium Is Vulnerable to Infarction and Refractory to Erythropoietin-Induced Protection"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855568561824256","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effect of kidney failure and hemodialysis on protein and amino acid metabolism"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855568645004544","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chronic kidney disease and cardiovascular complications"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569362894592","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mammalian Target of Rapamycin Signaling in Cardiac Physiology and Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569796201216","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Renal insufficiency and anemia are independent risk factors for death among patients with acute myocardial infarction1,21As published material, the contents of this manuscript may not be cited, quoted, reproduced or published without the consent of the authors.2The analyses upon which this publication is based were performed under Contract Number 500-96-P704, entitled “Operation Utilization and Quality Control Peer Review Organization (PRO) for the State of Georgia” and sponsored by the Centers for Medicare and Medicaid Services (CMS), Department of Health and Human Services. The conclusions and opinions expressed, and methods used herein are those of the authors. They do not necessarily reflect CMS policy. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by CMS, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this Contractor. Ideas and contributions to the authors concerning experience in engaging with issues presented are welcomed."}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593738420608","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of Erythropoiesis-Stimulating Agents in Cardiovascular Protection in CKD Patients: Reappraisal of Their Impact and Mechanisms"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044910926592","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular Basis of Cardioprotection"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518432310656","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Increased myocardial ischemia-reperfusion injury in renal failure involves cardiac adiponectin signal deficiency"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518927148800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effect of insulin and glucose infusion on myocardial infarction size in uraemic rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519293675776","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Endoplasmic Reticulum Stress in Diabetic Hearts Abolishes Erythropoietin-Induced Myocardial Protection by Impairment of Phospho–Glycogen Synthase Kinase-3β–Mediated Suppression of Mitochondrial Permeability Transition"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468342627840","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alteration in Erythropoietin-Induced Cardioprotective Signaling by Postinfarct Ventricular Remodeling"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981469053908864","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mitochondrial dysfunction in uremic cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943382459904","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ischemic Conditioning Protects the Uremic Heart in a Rodent Model of Myocardial Infarction"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943649240192","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regulation of Phosphorylation of Thr-308 of Akt, Cell Proliferation, and Survival by the B55α Regulatory Subunit Targeting of the Protein Phosphatase 2A Holoenzyme to Akt"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944977147520","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ser9 phosphorylation of mitochondrial GSK-3β is a primary mechanism of cardiomyocyte protection by erythropoietin against oxidant-induced apoptosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418457071488","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418664096512","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Increased Infarct Size in Uremic Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544418727747456","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Glycogen synthase kinase-3β mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544420294875904","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Short Communication: Angiotensin II Type 1 Receptor–Mediated Upregulation of Calcineurin Activity Underlies Impairment of Cardioprotective Signaling in Diabetic Hearts"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421409683456","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Progression of heart failure after myocardial infarction in the rat"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843920628096","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effect of Kidney Disease on Acute Coronary Syndrome"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844995177856","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Live-cell Molecular Analysis of Akt Activation Reveals Roles for Activation Loop Phosphorylation"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670318638256256","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Uremic cardiomyopathy is characterized by loss of the cardioprotective effects of 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