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http://purl.uniprot.org/citations/29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29388468http://www.w3.org/2000/01/rdf-schema#comment"Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in pulmonary arteries, but not in mesenteric arteries. Hypoxia caused a large increase in [Ca2+]i in PASMCs, which is diminished by the PLC inhibitor U73122 and not by its inactive analog U73433 . Hypoxia augments PLCγ1-dependent inositol 1,4,5-trisphosphate (IP3) generation. Exogenous ROS, hydrogen peroxide (H2O2), increases PLCγ1 phosphorylation at tyrosine-783 and IP3 production. IP3 receptor-1 (IP3R1) knock-down remarkably diminishes hypoxia- or H2O2-induced increase in [Ca2+]i. Hypoxia or H2O2 increases the activity of IP3Rs, which is significantly reduced in protein kinase C-ε (PKCε) knockout PASMCs. A higher PLCγ1 expression, activity, and basal [Ca2+]i are found in PASMCs, but not in mesenteric artery smooth muscle cells from mice exposed to chronic hypoxia (CH) for 21 days. CH enhances H2O2- and ATP-induced increase in [Ca2+]i in PASMCs and PLC-dependent, norepinephrine-evoked pulmonary vasoconstriction. In conclusion, acute hypoxia uniquely causes ROS-dependent PLCγ1 activation, IP3 production, PKCε activation, IP3R1 opening, Ca2+ release, and contraction in mouse PASMCs; CH enhances PASM PLCγ1 expression, activity, and function, playing an essential role in pulmonary hypertension in mice."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.org/dc/terms/identifier"doi:10.1152/ajplung.00243.2017"xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Joseph L."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Wang Y.X."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Song T."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Mei L."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Zheng Y.M."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/author"Yadav V.R."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/name"Am J Physiol Lung Cell Mol Physiol"xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/pages"L724-L735"xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/title"PLCgamma1-PKCepsilon-IPpisub>3pi/sub>R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells."xsd:string
http://purl.uniprot.org/citations/29388468http://purl.uniprot.org/core/volume"314"xsd:string
http://purl.uniprot.org/citations/29388468http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29388468
http://purl.uniprot.org/citations/29388468http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29388468
http://purl.uniprot.org/uniprot/#_A0A0N4SVN2-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_A0A0N4SW22-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_A0A0N4SWH7-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_A0A0N4SWI0-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_A0A1D5RLA1-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_A2A4A6-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_G3UXP4-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_F1DGF6-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468
http://purl.uniprot.org/uniprot/#_G3V016-mappedCitation-29388468http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29388468