Linked Life Data

21763292

Source:http://linkedlifedata.com/resource/pubmed/id/21763292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-8-15
pubmed:abstractText
High mobility group box (HMGB)-1 plays an important role in sepsis-associated death in experimental studies. Heme oxygenase-1 (HO-1) inducers were reported to reduce HMGB1 release in experimental sepsis. Previously, we reported on the importance of the ??-adrenergic receptor and protein kinase A pathway in the regulation of HO-1 expression by isoproterenol (ISO) in RAW 264.7 cells. We investigated whether ISO reduces HMGB1 release in LPS-activated RAW 264.7 cells and improves survival rate in septic mice due to HO-1 induction. ISO concentration-dependently increased HO-1 via Nrf-2 translocation and inhibited release of HMGB1 through the ??-adrenergic receptor (??-AR) in LPS-activated RAW 264.7 cells. This conclusion was supported by the finding that dobutamine but not salbutamol increased HO-1 expression in both RAW 264.7 cells. ISO failed to inhibit HMGB1 release when HO-1 expression was suppressed by ZnPPIX, an HO-1 inhibitor in RAW 264.7 cells. ISO significantly inhibited phosphorylation of I?B-? and NF-?B-driven luciferase activity in LPS-activated RAW 264.7 cells. In addition, LY294002, a PI3K inhibitor, and SB203580, a p38 MAPK inhibitor, significantly inhibited not only HO-1 induction but also HMGB1 release by ISO. Importantly, ISO increased HO-1 protein expression in heart and lung tissues, reduced HMGB1 in plasma and increased survival rate in CLP-treated septic mice, which was significantly reversed by co-treatment with ZnPPIX. Taken together, we conclude that inhibition of HMGB1 release during sepsis via ??-AR-mediated HO-1 induction is a novel mechanism for the beneficial effects of ISO in the treatment of sepsis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
769-77
pubmed:meshHeading
pubmed-meshheading:21763292-Animals, pubmed-meshheading:21763292-Cecum, pubmed-meshheading:21763292-Cell Line, pubmed-meshheading:21763292-Constriction, Pathologic, pubmed-meshheading:21763292-HMGB1 Protein, pubmed-meshheading:21763292-Heme Oxygenase-1, pubmed-meshheading:21763292-I-kappa B Kinase, pubmed-meshheading:21763292-Isoproterenol, pubmed-meshheading:21763292-Ligation, pubmed-meshheading:21763292-Lipopolysaccharides, pubmed-meshheading:21763292-Lung, pubmed-meshheading:21763292-Male, pubmed-meshheading:21763292-Mice, pubmed-meshheading:21763292-Mice, Inbred BALB C, pubmed-meshheading:21763292-Myocardium, pubmed-meshheading:21763292-NF-E2-Related Factor 2, pubmed-meshheading:21763292-NF-kappa B, pubmed-meshheading:21763292-Phosphatidylinositol 3-Kinases, pubmed-meshheading:21763292-Phosphorylation, pubmed-meshheading:21763292-Protein Transport, pubmed-meshheading:21763292-Punctures, pubmed-meshheading:21763292-Receptors, Adrenergic, beta-1, pubmed-meshheading:21763292-Sepsis, pubmed-meshheading:21763292-Survival Rate, pubmed-meshheading:21763292-p38 Mitogen-Activated Protein Kinases
pubmed:year
2011
pubmed:articleTitle
??-adrenergic receptor-mediated HO-1 induction, via PI3K and p38 MAPK, by isoproterenol in RAW 264.7 cells leads to inhibition of HMGB1 release in LPS-activated RAW 264.7 cells and increases in survival rate of CLP-induced septic mice.
pubmed:affiliation
Department of Pharmacology School of Medicine, and Institute of Health Sciences, Gyeongsang National University, Jinju 660-290, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't