Linked Life Data

17094942

Source:http://linkedlifedata.com/resource/pubmed/id/17094942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-11-19
pubmed:abstractText
Tumor necrosis factor-alpha (TNF-alpha) is implicated in heart failure and cardiomyocytes themselves can express TNF-alpha. Nevertheless, the mechanisms and regulations of TNF-alpha expression in cardiomyocytes remain poorly understood. The present study was to investigate the effects of simvastatin on TNF-alpha expression in cardiomyocytes and the underlying molecular mechanisms. In neonatal rat cardiomyocytes, RT-PCR and ELISA showed lipopolysaccharide (LPS)-induced TNF-alpha expression was attenuated by simvastatin pretreatment in a dose-dependent manner. The reactive oxygen species (ROS) scavenger N-acetylcysteine and the NADPH oxidase inhibitor diphenyleneiodonium also inhibited the LPS-induced expression of TNF-alpha. Dichlorofluorescein-fluorescence and cytochrome c reduction assay indicated LPS increased ROS generation and NADPH oxidase activity in cardiomyocytes, which were abrogated by simvastatin. Furthermore, similar to LPS, exogenous hydrogen peroxide also increased TNF-alpha secretion, but simvastatin did not significantly affect the hydrogen peroxide-induced TNF-alpha secretion. All the effects of simvastatin as mentioned above were completely reversed by concomitant pretreatment with mevalonate, a key intermediate during cholesterol synthesis. These results suggest that simvastatin attenuates LPS-induced TNF-alpha expression in cardiomyocytes via inhibition of activation of NADPH oxidase and subsequent ROS generation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine, http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Mevalonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase, http://linkedlifedata.com/resource/pubmed/chemical/Onium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Simvastatin, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/diphenyleneiodonium
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
351
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
947-52
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Simvastatin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiomyocytes: The role of reactive oxygen species.
pubmed:affiliation
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
pubmed:publicationType
Journal Article