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http://purl.uniprot.org/citations/20306336http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20306336http://www.w3.org/2000/01/rdf-schema#comment"Increases in heme oxygenase-1 (HO-1) and administration of heme degradation products CO and biliverdin inhibit vascular inflammation and vasoocclusion in mouse models of sickle cell disease (SCD). In this study, an albumin (alb) promoter-driven Sleeping Beauty (SB) transposase plasmid with a wild-type rat hmox-1 (wt-HO-1) transposable element was delivered by hydrodynamic tail vein injections to SCD mice. Eight weeks after injection, SCD mice had three-to five-fold increases in HO-1 activity and protein expression in liver, similar to hemin-treated mice. Immunohistochemistry demonstrated increased perinuclear HO-1 staining in hepatocytes. Messenger RNA transcription of the hmox-1 transgene in liver was confirmed by quantitative real-time polymerase chain reaction restriction fragment length polymorphism (qRT-PCR RFLP) with no detectible transgene expression in other organs. The livers of all HO-1 overexpressing mice had activation of nuclear phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-Akt, decreased nuclear expression of nuclear factor-kappa B (NF-kappaB) p65, and decreased soluble vascular cell adhesion molecule-1 (sVCAM-1) in serum. Hypoxia-induced stasis, a characteristic of SCD, but not normal mice, was inhibited in dorsal skin fold chambers in wt-HO-1 SCD mice despite the absence of hmox-1 transgene expression in the skin suggesting distal effects of HO activity on the vasculature. No protective effects were seen in SCD mice injected with nonsense (ns-) rat hmox-1 that encodes carboxy-truncated HO-1 with little or no enzyme activity. We speculate that HO-1 gene delivery to the liver is beneficial in SCD mice by degrading pro-oxidative heme, releasing anti-inflammatory heme degradation products CO and biliverdin/bilirubin into circulation, activating cytoprotective pathways and inhibiting vascular stasis at sites distal to transgene expression."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.org/dc/terms/identifier"doi:10.1007/s00109-010-0613-6"xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Chen C."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Nguyen J."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Steer C.J."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Vercellotti G.M."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Belcher J.D."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Beckman J.D."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Bruzzone C.M."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/author"Vineyard J.V."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/name"J Mol Med (Berl)"xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/pages"665-675"xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/title"Heme oxygenase-1 gene delivery by Sleeping Beauty inhibits vascular stasis in a murine model of sickle cell disease."xsd:string
http://purl.uniprot.org/citations/20306336http://purl.uniprot.org/core/volume"88"xsd:string
http://purl.uniprot.org/citations/20306336http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20306336
http://purl.uniprot.org/citations/20306336http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20306336
http://purl.uniprot.org/uniprot/#_A0A8L2UJE9-mappedCitation-20306336http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20306336
http://purl.uniprot.org/uniprot/#_P06762-mappedCitation-20306336http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20306336
http://purl.uniprot.org/uniprot/A0A8L2UJE9http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20306336
http://purl.uniprot.org/uniprot/P06762http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20306336