Source:http://linkedlifedata.com/resource/pubmed/id/17326158
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2007-3-5
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| pubmed:abstractText |
We previously reported that exogenous cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, exerts hepatoprotective effects. Because CT-1 is expressed in the normal liver, we hypothesized that this cytokine may constitute an endogenous defense of the liver against proapoptotic stimuli. Here, we found that CT-1-/- mice died faster than wild-type animals after challenge with a lethal dose of the Fas agonist Jo-2. At sublethal doses of Jo-2, all wild-type mice survived whereas CT-1-/- animals developed extensive hepatocyte apoptosis with 50% mortality at 24 hours. Pretreatment with CT-1 improved survival and reduced injury in both CT-1-/- and wild-type animals. Upon Fas ligation the activation of STAT-3, a molecule that defends the liver against apoptosis, was lower in CT-1-/- mice than in wild-type animals despite similar IL-6 up-regulation in the 2 groups. Analysis of liver transcriptome in CT-1-/- and wild-type mice showed that 9 genes reported to be associated with cell survival/death functions were differentially expressed in the 2 groups. Four of these genes [IGFBP1, peroxiredoxin3, TNFR1, and calpastatin (endogenous inhibitor of calpain)] could be validated by real-time PCR. All of them were down-regulated in CT-1-/- mice and were modulated by CT-1 administration. Treatment of CT-1-/- animals with the calpain inhibitor MDL28170 afforded significant protection against Fas-induced liver injury. CONCLUSION: CT-1-/- mice are highly sensitive to Fas-mediated apoptosis due in part to deficient STAT-3 activation and inadequate control of calpain activity during the apoptotic process. Our data show that CT-1 is a natural defense of the liver against apoptosis. This cytokine may have therapeutic potential.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Fas protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxin III,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Prdx3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/calpastatin,
http://linkedlifedata.com/resource/pubmed/chemical/cardiotrophin 1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
|
| pubmed:issn |
0270-9139
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
45
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
639-48
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:17326158-Animals,
pubmed-meshheading:17326158-Antibodies,
pubmed-meshheading:17326158-Antigens, CD95,
pubmed-meshheading:17326158-Apoptosis,
pubmed-meshheading:17326158-Calcium-Binding Proteins,
pubmed-meshheading:17326158-Cytokines,
pubmed-meshheading:17326158-Gene Expression Regulation,
pubmed-meshheading:17326158-Hepatocytes,
pubmed-meshheading:17326158-Liver,
pubmed-meshheading:17326158-Male,
pubmed-meshheading:17326158-Mice,
pubmed-meshheading:17326158-Mice, Inbred C57BL,
pubmed-meshheading:17326158-Mice, Knockout,
pubmed-meshheading:17326158-Peroxidases,
pubmed-meshheading:17326158-Peroxiredoxin III,
pubmed-meshheading:17326158-Peroxiredoxins,
pubmed-meshheading:17326158-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:17326158-STAT3 Transcription Factor
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| pubmed:year |
2007
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| pubmed:articleTitle |
Cardiotrophin-1 is an essential factor in the natural defense of the liver against apoptosis.
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| pubmed:affiliation |
Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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