Linked Life Data

21186276

Source:http://linkedlifedata.com/resource/pubmed/id/21186276

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-3
pubmed:abstractText
High-mobility group box 1 (HMGB1) is a nuclear protein that has been implicated in the myocardial inflammation and injury induced by ischemia-reperfusion (I/R). The purpose of the present study was to assess the role of HMGB1 in myocardial apoptosis induced by I/R. In vivo, myocardial I/R induced an increase in myocardial HMGB1 expression and apoptosis. Inhibition of HMGB1 (A-box) ameliorated the I/R-induced myocardial apoptosis. In vitro, isolated cardiac myocytes were challenged with anoxia-reoxygenation (A/R; in vitro correlate to I/R). A/R-challenged myocytes also generated HMGB1 and underwent apoptosis. Inhibition of HMGB1 attenuated the A/R-induced myocyte apoptosis. Exogenous HMGB1 had no effect on myocyte apoptosis. However, inhibition of HMGB1 attenuated myocyte TNF-? production after the A/R was challenged; surprisingly, HMGB1 itself did not induce myocyte TNF-? production. Exogenous TNF-? induced a moderate proapoptotic effect on the myocytes, an effect substantially potentiated by coadministration of HMGB1. It is generally accepted that apoptosis induced by TNF-? is regulated by the balance of activation of c-Jun NH(2)-terminal kinase (JNK) and NF-?B. Indeed, in the present study, TNF-? increased the phosphorylation status of JNK and p65, a subunit of NF-?B; HMGB1 greatly potentiated TNF-?-induced JNK phosphorylation. Furthermore, inhibition of JNK (SP-600125) prevented the myocyte apoptosis induced by a TNF-?/HMGB1 cocktail. Finally, A/R increased HMGB1 production in both wild-type and toll-like receptor 4-deficient myocytes; however, deficiency in toll-like receptor 4 diminished A/R-induced myocyte apoptosis, TNF-?, and JNK activation. Our results indicate that myocyte-derived HMGB1 and TNF-? work in concert to promote I/R-induced myocardial apoptosis through JNK activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H913-21
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Endogenous HMGB1 contributes to ischemia-reperfusion-induced myocardial apoptosis by potentiating the effect of TNF-α/JNK.
pubmed:affiliation
Critical Illness Research, Lawson Health Research Institute, 800 Commissioners Road E, VRL Rm A6-138, London, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural