Source:http://linkedlifedata.com/resource/pubmed/id/11264281
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
|
| pubmed:dateCreated |
2001-6-4
|
| pubmed:abstractText |
Mitochondrial levels of the anti-oxidant enzyme, manganese superoxide dismutase (MnSOD), are dramatically elevated in response to stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and lipopolysaccharide (LPS). However, the precise intracellular signaling pathways responsible for this inducible expression are poorly understood. MnSOD expression in pulmonary epithelial and endothelial cells, treated with inflammatory mediators and various inhibitors, was studied by Northern analysis. The mitochondrial electron transport chain inhibitors, antimycin A and myxothiazol, selectively blocked TNF-alpha-inducible expression of MnSOD but not that of IL-1beta or LPS, indicating different signaling pathways. N-Acetylcysteine could reliably decrease inducible MnSOD expression by TNF-alpha, but not IL-1, linking reactive oxygen species (ROS) to the TNF-alpha signaling pathway. Elevated levels of arachidonic acid have been demonstrated previously to generate mitochondrial ROS. A specific cytoplasmic phospholipase A(2) inhibitor reduced stimulated MnSOD expression by TNF-alpha, but not by IL-1beta, further supporting the role of ROS. Other investigators have shown that MnSOD expression may be regulated by NF-kappaB. Our results with a specific inhibitory kappa-kinase inhibitor indicate that NF-kappaB modulates IL-1beta signaling but not the TNF-alpha pathway. Thus, we have demonstrated that although inducible MnSOD transcription may appear similar at the messenger RNA level, the intracellular signaling pathways are differentially regulated.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimycin A,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
8
|
| pubmed:volume |
276
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
20419-27
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:11264281-Animals,
pubmed-meshheading:11264281-Antimycin A,
pubmed-meshheading:11264281-Cell Line,
pubmed-meshheading:11264281-Cell Nucleus,
pubmed-meshheading:11264281-Cytoplasm,
pubmed-meshheading:11264281-Electron Transport,
pubmed-meshheading:11264281-Endothelium,
pubmed-meshheading:11264281-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:11264281-Humans,
pubmed-meshheading:11264281-Interleukin-1,
pubmed-meshheading:11264281-Lipopolysaccharides,
pubmed-meshheading:11264281-Lung,
pubmed-meshheading:11264281-Mitochondria,
pubmed-meshheading:11264281-Phospholipases A,
pubmed-meshheading:11264281-Rats,
pubmed-meshheading:11264281-Recombinant Proteins,
pubmed-meshheading:11264281-Signal Transduction,
pubmed-meshheading:11264281-Superoxide Dismutase,
pubmed-meshheading:11264281-Tumor Necrosis Factor-alpha
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
Tumor necrosis factor-alpha selectively induces MnSOD expression via mitochondria-to-nucleus signaling, whereas interleukin-1beta utilizes an alternative pathway.
|
| pubmed:affiliation |
Departments of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
|
| pubmed:publicationType |
Journal Article
|