{"@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/1361699995582978560.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1161/01.res.87.5.385"}},{"identifier":{"@type":"URI","@value":"https://www.ahajournals.org/doi/full/10.1161/01.RES.87.5.385"}},{"identifier":{"@type":"PMID","@value":"10969036"}}],"dc:title":[{"@value":"Fluid Shear Stress Activates Ca<sup>2+</sup>Influx Into Human Endothelial Cells via P2X4 Purinoceptors"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p><jats:italic>Abstract</jats:italic>—Ca<jats:sup>2+</jats:sup>signaling plays an important role in endothelial cell (EC) responses to shear stress generated by blood flow. Our previous studies demonstrated that bovine fetal aortic ECs showed a shear stress–dependent Ca<jats:sup>2+</jats:sup>influx when exposed to flow in the presence of extracellular ATP. However, the molecular mechanisms of this process, including the ion channels responsible for the Ca<jats:sup>2+</jats:sup>response, have not been clarified. Here, we demonstrate that P2X4 purinoceptors, a subtype of ATP-operated cation channels, are involved in the shear stress–mediated Ca<jats:sup>2+</jats:sup>influx. Human umbilical vein ECs loaded with the Ca<jats:sup>2+</jats:sup>indicator Indo-1/AM were exposed to laminar flow of Hanks’ balanced salt solution at various concentrations of ATP, and changes in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>were monitored with confocal laser scanning microscopy. A stepwise increase in shear stress elicited a corresponding stepwise increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>at 250 nmol/L ATP. The shear stress–dependent increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>was not affected by phospholipase C inhibitor (U-73122) but disappeared after the chelation of extracellular Ca<jats:sup>2+</jats:sup>with EGTA, indicating that the Ca<jats:sup>2+</jats:sup>increase was due to Ca<jats:sup>2+</jats:sup>influx. Antisense oligonucleotides designed to knockout P2X4 expression abolished the shear stress–dependent Ca<jats:sup>2+</jats:sup>influx seen at 250 nmol/L ATP in human umbilical vein ECs. Human embryonic kidney 293 cells showed no Ca<jats:sup>2+</jats:sup>response to flow at 2 μmol/L ATP, but when transfected with P2X4 cDNA, they began to express P2X4 purinoceptors and to show shear stress–dependent Ca<jats:sup>2+</jats:sup>influx. P2X4 purinoceptors may have a “shear-transducer” property through which shear stress is perceived directly or indirectly and transmitted into the cell interior via Ca<jats:sup>2+</jats:sup>signaling.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699995582978433","@type":"Researcher","foaf:name":[{"@value":"Kimiko Yamamoto"}],"jpcoar:affiliationName":[{"@value":"From the Department of Biomedical Engineering (K.Y., R.K., J.A.), Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and Interdisciplinary Science Center (A.K.), Nihon University, Tokyo, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995582978560","@type":"Researcher","foaf:name":[{"@value":"Risa Korenaga"}],"jpcoar:affiliationName":[{"@value":"From the Department of Biomedical Engineering (K.Y., R.K., J.A.), Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and Interdisciplinary Science Center (A.K.), Nihon University, Tokyo, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995582978432","@type":"Researcher","foaf:name":[{"@value":"Akira Kamiya"}],"jpcoar:affiliationName":[{"@value":"From the Department of Biomedical Engineering (K.Y., R.K., J.A.), Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and Interdisciplinary Science Center (A.K.), Nihon University, Tokyo, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995582978434","@type":"Researcher","foaf:name":[{"@value":"Joji Ando"}],"jpcoar:affiliationName":[{"@value":"From the Department of Biomedical Engineering (K.Y., R.K., J.A.), Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and Interdisciplinary Science Center (A.K.), Nihon University, Tokyo, Japan."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00097330"},{"@type":"EISSN","@value":"15244571"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00097330"}],"prism:publicationName":[{"@value":"Circulation Research"}],"dc:publisher":[{"@value":"Ovid Technologies (Wolters Kluwer Health)"}],"prism:publicationDate":"2000-09","prism:volume":"87","prism:number":"5","prism:startingPage":"385","prism:endingPage":"391"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.ahajournals.org/doi/full/10.1161/01.RES.87.5.385"}],"createdAt":"2012-06-12","modifiedAt":"2025-03-30","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Umbilical%20Veins","dc:title":"Umbilical Veins"},{"@id":"https://cir.nii.ac.jp/all?q=Indoles","dc:title":"Indoles"},{"@id":"https://cir.nii.ac.jp/all?q=Microscopy,%20Confocal","dc:title":"Microscopy, Confocal"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Purinergic%20P2","dc:title":"Receptors, Purinergic P2"},{"@id":"https://cir.nii.ac.jp/all?q=Oligonucleotides,%20Antisense","dc:title":"Oligonucleotides, Antisense"},{"@id":"https://cir.nii.ac.jp/all?q=Transfection","dc:title":"Transfection"},{"@id":"https://cir.nii.ac.jp/all?q=Pyrrolidinones","dc:title":"Pyrrolidinones"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Adenosine%20Triphosphate","dc:title":"Adenosine Triphosphate"},{"@id":"https://cir.nii.ac.jp/all?q=Type%20C%20Phospholipases","dc:title":"Type C Phospholipases"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium","dc:title":"Calcium"},{"@id":"https://cir.nii.ac.jp/all?q=Calcium%20Signaling","dc:title":"Calcium Signaling"},{"@id":"https://cir.nii.ac.jp/all?q=Endothelium,%20Vascular","dc:title":"Endothelium, Vascular"},{"@id":"https://cir.nii.ac.jp/all?q=Stress,%20Mechanical","dc:title":"Stress, Mechanical"},{"@id":"https://cir.nii.ac.jp/all?q=Estrenes","dc:title":"Estrenes"},{"@id":"https://cir.nii.ac.jp/all?q=Rheology","dc:title":"Rheology"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Purinergic%20P2X4","dc:title":"Receptors, Purinergic P2X4"},{"@id":"https://cir.nii.ac.jp/all?q=Cells,%20Cultured","dc:title":"Cells, Cultured"},{"@id":"https://cir.nii.ac.jp/all?q=Fluorescent%20Dyes","dc:title":"Fluorescent Dyes"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050022708918899456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004233534748800","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The P2X4 receptor is required for neuroprotection via 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