Loading...
Please wait, while we are loading the content...
Similar Documents
Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and mediates the protective effect of ischemic preconditioning
| Content Provider | Semantic Scholar |
|---|---|
| Author | Iñiguez, María Berasain, Carmen Martínez-Ansó, Eduardo Bustos, Matilde Fortes, Puri Pennica, Diane Avila, Matías A. Prieto, Jesús |
| Copyright Year | 2006 |
| Abstract | Ischemia-reperfusion (I/R) liver injury occurs when blood flow is restored after prolonged ischemia. A short interruption of blood flow (ischemic preconditioning [IP]) induces tolerance to subsequent prolonged ischemia through ill-defined mechanisms. Cardiotrophin (CT)-1, a cytokine of the interleukin-6 family, exerts hepatoprotective effects and activates key survival pathways like JAK/STAT3. Here we show that administration of CT-1 to rats or mice protects against I/R liver injury and that CT-1-deficient mice are exceedingly sensitive to this type of damage. IP markedly reduced transaminase levels and abrogated caspase-3 and c-Jun-NH2-terminal kinase activation after I/R in normal mice but not in CT-1-null mice. Moreover, the protective effect afforded by IP was reduced by previous administration of neutralizing anti-CT-1 antibody. Prominent STAT3 phosphorylation in liver tissue was observed after IP plus I/R in normal mice but not in CT-1-null mice. Oxidative stress, a process involved in IP-induced hepatoprotection, was found to stimulate CT-1 release from isolated hepatocytes. Interestingly, brief ischemia followed by short reperfusion caused mild serum transaminase elevation and strong STAT3 activation in normal and IL-6-deficient mice, but failed to activate STAT3 and provoked marked hypertransaminasemia in CT-1-null animals. In conclusion, CT-1 is an essential endogenous defense of the liver against I/R and is a key mediator of the protective effect induced by IP. |
| Starting Page | 2809 |
| Ending Page | 2815 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 17178916v1 |
| Volume Number | 203 |
| Journal | The Journal of experimental medicine |
| Alternate Webpage(s) | http://jem.rupress.org/content/jem/203/13/2809.full.pdf |
| Alternate Webpage(s) | http://dadun.unav.edu/bitstream/10171/20306/1/2809.full.pdf |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/08/jem2032809.PMC2118168.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Activation action Cerebral Ischemia Chemical and Drug Induced Liver Injury Hypoxic-Ischemic Encephalopathy Immunoprecipitation Liver parenchyma Mediator brand of benfluorex hydrochloride Oxidative Stress Physiological reperfusion Reperfusion Injury Reperfusion Therapy Transaminases Transient Ischemic Attack cardiotrophin 1 caspase-3 cytokine |
| Content Type | Text |
| Resource Type | Article |
