| http://purl.uniprot.org/citations/22046279 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22046279 | http://www.w3.org/2000/01/rdf-schema#comment | "Carbon monoxide (CO) dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ) and p38 mitogen-activated protein kinase (MAPK) dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS)-induced expression of the proinflammatory early growth response-1 (Egr-1) transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2). Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-)), produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0026376"xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Bilban M."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Esterbauer H."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Wagner O."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Haschemi A."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Otterbein L.E."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Chin B.Y."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/author | "Jeitler M."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/pages | "e26376"xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/title | "Carbon monoxide induced PPARgamma SUMOylation and UCP2 block inflammatory gene expression in macrophages."xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/22046279 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22046279 |
| http://purl.uniprot.org/citations/22046279 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22046279 |
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| http://purl.uniprot.org/uniprot/#_Q9R246-mappedCitation-22046279 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22046279 |