{"@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/1363670320805080448.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.162100799"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.162100799"}}],"dc:title":[{"@value":"Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            Recent investigation has focused on identifying signaling pathways that inhibit cardiac hypertrophy, a major risk factor for cardiovascular morbidity and mortality. In this context, nitric oxide (NO), signaling via cGMP and cGMP-dependent protein kinase type I (PKG I), has been recognized as a negative regulator of cardiac myocyte (CM) hypertrophy. However, the underlying mechanisms are poorly understood. Here, we show that PKG I inhibits CM hypertrophy by targeting the calcineurin-NFAT signaling pathway. Calcineurin, a Ca\n            <jats:sup>2+</jats:sup>\n            -dependent phosphatase, promotes hypertrophy in part by activating NFAT transcription factors which induce expression of hypertrophic genes, including brain natriuretic peptide (BNP). Activation of PKG I by NO/cGMP in CM suppressed NFAT transcriptional activity, BNP induction, and cell enlargement in response to α\n            <jats:sub>1</jats:sub>\n            -adrenoreceptor stimulation but not in response to adenoviral expression of a Ca\n            <jats:sup>2+</jats:sup>\n            -independent, constitutively active calcineurin mutant, thus demonstrating NO-cGMP-PKG I inhibition of calcineurin-NFAT signaling upstream of calcineurin. PKG I suppressed single L-type Ca\n            <jats:sup>2+</jats:sup>\n            -channel open probability, [Ca\n            <jats:sup>2+</jats:sup>\n            ]\n            <jats:sub>i</jats:sub>\n            transient amplitude, and, most importantly, L-type Ca\n            <jats:sup>2+</jats:sup>\n            -channel current-induced NFAT activation, indicating that PKG I targets Ca\n            <jats:sup>2+</jats:sup>\n            -dependent steps upstream of calcineurin. Adenoviral expression of PKG I enhanced NO/cGMP inhibitory effects upstream of calcineurin, confirming that PKG I mediates NO/cGMP inhibition of calcineurin-NFAT signaling. In CM overexpressing PKG I, NO/cGMP also suppressed BNP induction and cell enlargement but not NFAT activation elicited by constitutively active calcineurin, which is consistent with additional, NFAT-independent inhibitory effect(s) of PKG I downstream of calcineurin. Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380294721755889794","@type":"Researcher","foaf:name":[{"@value":"Beate Fiedler"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889792","@type":"Researcher","foaf:name":[{"@value":"Suzanne M. Lohmann"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889795","@type":"Researcher","foaf:name":[{"@value":"Albert Smolenski"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889793","@type":"Researcher","foaf:name":[{"@value":"Stephan Linnemüller"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889796","@type":"Researcher","foaf:name":[{"@value":"Burkert Pieske"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889798","@type":"Researcher","foaf:name":[{"@value":"Frank Schröder"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889797","@type":"Researcher","foaf:name":[{"@value":"Jeffery D. Molkentin"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889800","@type":"Researcher","foaf:name":[{"@value":"Helmut Drexler"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294721755889799","@type":"Researcher","foaf:name":[{"@value":"Kai C. Wollert"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany; Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany; Department of Cardiology and Pneumology, University of Göttingen, 37075 Göttingen, Germany; and Department of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039"}]}],"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":"2002-08-12","prism:volume":"99","prism:number":"17","prism:startingPage":"11363","prism:endingPage":"11368"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.162100799"}],"createdAt":"2002-09-30","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004236433102720","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Inhibition of TRPC6 Channel Activity Contributes to the Antihypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart"}]},{"@id":"https://cir.nii.ac.jp/crid/1360009142769119744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285708952930688","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Phosphorylation of TRPC6 Channels at Thr69 Is Required for Anti-hypertrophic Effects of Phosphodiesterase 5 Inhibition"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567189411561344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"TRPC5-eNOS Axis Negatively Regulates ATP-Induced Cardiomyocyte Hypertrophy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588379379180288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Endothelial eNOS deficiency causes podocyte injury through NFAT2 and heparanase in diabetic mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848662967139712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Regulation of cardiovascular TRP channel functions along the NO–cGMP–PKG axis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861704785424000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Physiological and Pathophysiological Effects of C-Type Natriuretic Peptide on the Heart"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204274078464","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Ca<sup>2+</sup>-mediated pathogenesis in the heart"},{"@value":"カルシウムにより惹起される心病態"},{"@language":"ja-Kana","@value":"カルシウム ニ ヨリ ジャッキ サレル シン ビョウタイ"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.162100799"},{"@type":"CROSSREF","@value":"10.1161/circresaha.109.208314_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.1254/fpj.140.270_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.1016/j.jjcc.2021.03.004_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.1074/jbc.m109.074104_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.3389/fphar.2018.00523_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.1038/s41598-024-79501-0_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.1586/ecp.10.15_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"},{"@type":"CROSSREF","@value":"10.3390/biology11060911_references_DOI_aNn6CPJBZqiGnILl0GhtRdwt8YZ"}]}