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http://purl.uniprot.org/citations/23596175http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23596175http://www.w3.org/2000/01/rdf-schema#comment"The function of dendritic cells (DCs), antigen-presenting cells regulating naïve T-cells, is regulated by cytosolic Ca²⁺ concentration ([Ca²⁺]i). [Ca²⁺]i is increased by store-operated Ca²⁺ entry and decreased by K⁺-independent (NCX) and K⁺-dependent (NCKX) Na⁺/Ca²⁺ exchangers. NCKX exchangers are stimulated by immunosuppressive 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃], the biologically active form of vitamin D. Formation of 1,25(OH)₂D₃ is inhibited by the antiaging protein Klotho. Thus 1,25(OH)₂D₃ plasma levels are excessive in Klotho-deficient mice (klothohm). The present study explored whether Klotho deficiency modifies [Ca²⁺]i regulation in DCs. DCs were isolated from the bone marrow of klothohm mice and wild-type mice (klotho+/+) and cultured for 7-9 days with granulocyte-macrophage colony-stimulating factor. According to major histocompatibility complex II (MHC II) and CD86 expression, differentiation and lipopolysaccharide (LPS)-induced maturation were similar in klothohm DCs and klotho+/+ DCs. However, NCKX1 membrane abundance and NCX/NCKX-activity were significantly enhanced in klothohm DCs. The [Ca²⁺]i increase upon acute application of LPS (1 μg/ml) was significantly lower in klothohm DCs than in klotho+/+ DCs, a difference reversed by the NCKX blocker 3',4'-dichlorobenzamyl (DBZ; 10 μM). CCL21-dependent migration was significantly less in klothohm DCs than in klotho+/+ DCs but could be restored by DBZ. NCKX activity was enhanced by pretreatment of klotho+/+ DC precursors with 1,25(OH)₂D₃ the first 2 days after isolation from bone marrow. Feeding klothohm mice a vitamin D-deficient diet decreased NCKX activity, augmented LPS-induced increase of [Ca²⁺]i, and enhanced migration of klothohm DCs, thus dissipating the differences between klothohm DCs and klotho+/+ DCs. In conclusion, Klotho deficiency upregulates NCKX1 membrane abundance and Na⁺/Ca²⁺-exchange activity, thus blunting the increase of [Ca²⁺]i following LPS exposure and CCL21-mediated migration. The effects are in large part due to excessive 1,25(OH)₂D₃ formation."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.org/dc/terms/identifier"doi:10.1152/ajpcell.00355.2012"xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Yang W."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Lang F."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Schmid E."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Russo A."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Kuro-o M."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Heise N."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Shumilina E."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Nurbaeva M.K."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Szteyn K."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Xuan N.T."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Faggio C."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/author"Leibrock C."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/name"Am J Physiol Cell Physiol"xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/pages"C70-7"xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/title"Altered regulation of cytosolic Ca^2⁺ concentration in dendritic cells from klotho hypomorphic mice."xsd:string
http://purl.uniprot.org/citations/23596175http://purl.uniprot.org/core/volume"305"xsd:string
http://purl.uniprot.org/citations/23596175http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23596175
http://purl.uniprot.org/citations/23596175http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23596175
http://purl.uniprot.org/uniprot/#_O35082-mappedCitation-23596175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23596175
http://purl.uniprot.org/uniprot/#_Q3UYK1-mappedCitation-23596175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23596175
http://purl.uniprot.org/uniprot/O35082http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23596175