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| pubmed-article:19450605 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:19450605 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:19450605 | pubmed:dateCreated | 2009-6-29 | lld:pubmed |
| pubmed-article:19450605 | pubmed:abstractText | The purpose of this study was to investigate the role of Rac1 and estrogen in sex difference of cardiac tumor necrosis factor-alpha (TNF-alpha) expression during endotoxemia. Endotoxemia was induced in male and female mice by peritoneal injection of lipopolysaccharide (LPS, 4 mg/kg). Compared with female mice, male mice produced more TNF-alpha in the heart 4 h after LPS treatment, which were correlated with higher Rac1 and NADPH oxidase activity, more phosphorylation of ERK1/2 and p38 MAPK, and up-regulation of toll-like receptor-4 (TLR-4) expression in male mice. Cardiac specific Rac1 knockout or administration of 17beta-estradiol down-regulated Rac1 expression, attenuated gp91(phox)-NADPH oxidase expression and activity, decreased phosphorylation of ERK1/2/p38 MAPK and inhibited cardiac TNF-alpha expression induced by LPS, suggesting an important role of Rac1 and estrogen in LPS-stimulated TNF-alpha expression in the heart. More importantly, the sex difference in TNF-alpha expression was abrogated by Rac1 knockout or gp91(phox) knockout and by administration of apocynin or N-acetylcysteine in LPS-stimulated mice. To investigate the functional significance of sex difference in endotoxemia, heart function was measured in isolated hearts with a Langendorff system. Male mice exhibited worse myocardial dysfunction compared with female in endotoxemia. Treatment of male mice with 17beta-estradiol attenuated myocardial dysfunction during endotoxemia. In conclusion, LPS induces Rac1 activation, which contributes to NADPH oxidase activity and phosphorylation of ERK1/2/p38 MAPK, leading to TNF-alpha expression in the heart. The sex difference in TNF-alpha expression is estrogen-dependent and mediated via Rac1 dependent NADPH oxidase/ERK1/2 and p38 MAPK pathway in LPS-stimulated hearts. | lld:pubmed |
| pubmed-article:19450605 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19450605 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19450605 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19450605 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19450605 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:19450605 | pubmed:issn | 1095-8584 | lld:pubmed |
| pubmed-article:19450605 | pubmed:author | pubmed-author:PengTianqingT | lld:pubmed |
| pubmed-article:19450605 | pubmed:author | pubmed-author:ShanLimeiL | lld:pubmed |
| pubmed-article:19450605 | pubmed:author | pubmed-author:ZhuHuaqingH | lld:pubmed |
| pubmed-article:19450605 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19450605 | pubmed:volume | 47 | lld:pubmed |
| pubmed-article:19450605 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19450605 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19450605 | pubmed:pagination | 264-74 | lld:pubmed |
| pubmed-article:19450605 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:19450605 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19450605 | pubmed:articleTitle | Rac1 mediates sex difference in cardiac tumor necrosis factor-alpha expression via NADPH oxidase-ERK1/2/p38 MAPK pathway in endotoxemia. | lld:pubmed |
| pubmed-article:19450605 | pubmed:affiliation | Critical Illness Research, Lawson Health Research Institute, London Health Sciences Center, London, Ontario, Canada. | lld:pubmed |
| pubmed-article:19450605 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19450605 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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