{"@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/1363670318979775488.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0609656104"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0609656104"}},{"identifier":{"@type":"PMID","@value":"17360381"}},{"identifier":{"@type":"HANDLE","@value":"2434/44525"}},{"identifier":{"@type":"HANDLE","@value":"11573/82150"}},{"identifier":{"@type":"NAID","@value":"80018618645"}}],"dc:title":[{"@value":"Genetic deletion of p66\n            <sup>Shc</sup>\n            adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            Increased production of reactive oxygen species (ROS) and loss of endothelial NO bioavailability are key features of vascular disease in diabetes mellitus. The p66\n            <jats:sup>Shc</jats:sup>\n            adaptor protein controls cellular responses to oxidative stress. Mice lacking p66\n            <jats:sup>Shc</jats:sup>\n            (p66\n            <jats:sup>Shc−/−</jats:sup>\n            ) have increased resistance to ROS and prolonged life span. The present work was designed to investigate hyperglycemia-associated changes in endothelial function in a model of insulin-dependent diabetes mellitus p66\n            <jats:sup>Shc−/−</jats:sup>\n            mouse. p66\n            <jats:sup>Shc−/−</jats:sup>\n            and wild-type (WT) mice were injected with citrate buffer (control) or made diabetic by an i.p. injection of 200 mg of streptozotocin per kg of body weight. Streptozotocin-treated p66\n            <jats:sup>Shc−/−</jats:sup>\n            and WT mice showed a similar increase in blood glucose. However, significant differences arose with respect to endothelial dysfunction and oxidative stress. WT diabetic mice displayed marked impairment of endothelium-dependent relaxations, increased peroxynitrite (ONOO\n            <jats:sup>−</jats:sup>\n            ) generation, nitrotyrosine expression, and lipid peroxidation as measured in the aortic tissue. In contrast, p66\n            <jats:sup>Shc−/−</jats:sup>\n            diabetic mice did not develop these high-glucose-mediated abnormalities. Furthermore, protein expression of the antioxidant enzyme heme oxygenase 1 and endothelial NO synthase were up-regulated in p66\n            <jats:sup>Shc−/−</jats:sup>\n            but not in WT mice. We report that p66\n            <jats:sup>Shc−/−</jats:sup>\n            mice are resistant to hyperglycemia-induced, ROS-dependent endothelial dysfunction. These data suggest that p66\n            <jats:sup>Shc</jats:sup>\n            adaptor protein is part of a signal transduction pathway relevant to hyperglycemia vascular damage and, hence, may represent a novel therapeutic target against diabetic vascular complications.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380857671174927616","@type":"Researcher","foaf:name":[{"@value":"Massimo Volpe"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Second Faculty of Medicine, University La Sapienza, 00189 Rome, Italy;"},{"@value":"IRCCS Neuromed, 86077 Pozzilli, Italy"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927618","@type":"Researcher","foaf:name":[{"@value":"PierGiuseppe Pelicci"}],"jpcoar:affiliationName":[{"@value":"Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927491","@type":"Researcher","foaf:name":[{"@value":"Piero Anversa"}],"jpcoar:affiliationName":[{"@value":"**New York Medical College, Cardiovascular Research Institute, Valhalla, NY 10595; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927493","@type":"Researcher","foaf:name":[{"@value":"Thomas F. Lüscher"}],"jpcoar:affiliationName":[{"@value":"*Cardiology and Cardiovascular Research, University Hospital, Zürich, Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927489","@type":"Researcher","foaf:name":[{"@value":"Francesco Cosentino"}],"jpcoar:affiliationName":[{"@value":"*Cardiology and Cardiovascular Research, University Hospital, Zürich, Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland;"},{"@value":"Division of Cardiology, Second Faculty of Medicine, University La Sapienza, 00189 Rome, Italy;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927495","@type":"Researcher","foaf:name":[{"@value":"Markus Bachschmid"}],"jpcoar:affiliationName":[{"@value":"Department of Biology, University of Konstanz, D-78457 Konstanz, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927488","@type":"Researcher","foaf:name":[{"@value":"Marzia Schiavoni"}],"jpcoar:affiliationName":[{"@value":"*Cardiology and Cardiovascular Research, University Hospital, Zürich, Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927492","@type":"Researcher","foaf:name":[{"@value":"Pietro Francia"}],"jpcoar:affiliationName":[{"@value":"Division of Cardiology, Second Faculty of Medicine, University La Sapienza, 00189 Rome, Italy;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927490","@type":"Researcher","foaf:name":[{"@value":"Giovanni G. Camici"}],"jpcoar:affiliationName":[{"@value":"*Cardiology and Cardiovascular Research, University Hospital, Zürich, Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927619","@type":"Researcher","foaf:name":[{"@value":"Ines Martin-Padura"}],"jpcoar:affiliationName":[{"@value":"Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927494","@type":"Researcher","foaf:name":[{"@value":"Martin Hersberger"}],"jpcoar:affiliationName":[{"@value":"Institute of Clinical Chemistry, University Hospital, CH-8057 Zürich, Switzerland;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857671174927617","@type":"Researcher","foaf:name":[{"@value":"Felix C. Tanner"}],"jpcoar:affiliationName":[{"@value":"*Cardiology and Cardiovascular Research, University Hospital, Zürich, Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland;"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1890583643101178250","@type":"Researcher","foaf:name":[{"@value":"University of Zurich"}]},{"@id":"https://cir.nii.ac.jp/crid/1890583643101178241","@type":"Researcher","foaf:name":[{"@value":"Cosentino, Francesco"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2007-03-20","prism:volume":"104","prism:number":"12","prism:startingPage":"5217","prism:endingPage":"5222"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0609656104"}],"createdAt":"2007-03-15","modifiedAt":"2022-04-12","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Luminescence","dc:title":"Luminescence"},{"@id":"https://cir.nii.ac.jp/all?q=Src%20Homology%202%20Domain-Containing,%20Transforming%20Protein%201","dc:title":"Src Homology 2 Domain-Containing, Transforming Protein 1"},{"@id":"https://cir.nii.ac.jp/all?q=Nitric%20Oxide%20Synthase%20Type%20III","dc:title":"Nitric Oxide Synthase Type III"},{"@id":"https://cir.nii.ac.jp/all?q=610%20Medicine%20%26%20health","dc:title":"610 Medicine & health"},{"@id":"https://cir.nii.ac.jp/all?q=In%20Vitro%20Techniques","dc:title":"In Vitro Techniques"},{"@id":"https://cir.nii.ac.jp/all?q=Thiobarbituric%20Acid%20Reactive%20Substances","dc:title":"Thiobarbituric Acid Reactive Substances"},{"@id":"https://cir.nii.ac.jp/all?q=Streptozocin","dc:title":"Streptozocin"},{"@id":"https://cir.nii.ac.jp/all?q=Diabetes%20Mellitus,%20Experimental","dc:title":"Diabetes Mellitus, Experimental"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Isometric%20Contraction","dc:title":"Isometric Contraction"},{"@id":"https://cir.nii.ac.jp/all?q=Peroxynitrous%20Acid","dc:title":"Peroxynitrous Acid"},{"@id":"https://cir.nii.ac.jp/all?q=540%20Chemistry","dc:title":"540 Chemistry"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Aorta","dc:title":"Aorta"},{"@id":"https://cir.nii.ac.jp/all?q=10038%20Institute%20of%20Clinical%20Chemistry","dc:title":"10038 Institute of Clinical Chemistry"},{"@id":"https://cir.nii.ac.jp/all?q=Adaptor%20Proteins,%20Signal%20Transducing","dc:title":"Adaptor Proteins, Signal Transducing"},{"@id":"https://cir.nii.ac.jp/all?q=1000%20Multidisciplinary","dc:title":"1000 Multidisciplinary"},{"@id":"https://cir.nii.ac.jp/all?q=Free%20Radical%20Scavengers","dc:title":"Free Radical Scavengers"},{"@id":"https://cir.nii.ac.jp/all?q=Vasomotor%20System","dc:title":"Vasomotor System"},{"@id":"https://cir.nii.ac.jp/all?q=Oxidative%20Stress","dc:title":"Oxidative Stress"},{"@id":"https://cir.nii.ac.jp/all?q=Shc%20Signaling%20Adaptor%20Proteins","dc:title":"Shc Signaling Adaptor Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Hyperglycemia","dc:title":"Hyperglycemia"},{"@id":"https://cir.nii.ac.jp/all?q=Endothelium,%20Vascular","dc:title":"Endothelium, Vascular"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Deletion","dc:title":"Gene Deletion"},{"@id":"https://cir.nii.ac.jp/all?q=Heme%20Oxygenase-1","dc:title":"Heme Oxygenase-1"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360565168607624192","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Novel role of p66Shc in ROS-dependent VEGF signaling and angiogenesis in endothelial cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1571980075650833920","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"活性酸素種に対する細胞応答に関わる遺伝子群について"},{"@language":"en","@value":"Toward a better understanding of genetic components that regulate cellular response to reactive oxygen species"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.0609656104"},{"@type":"CIA","@value":"80018618645"},{"@type":"OPENAIRE","@value":"doi_dedup___::9403145d8ddeeaf700aab3e773a97f9c"},{"@type":"CROSSREF","@value":"10.1152/ajpheart.00739.2011_references_DOI_K4R2d98mId91LlLsRYuM3BVIPmx"}]}