ag-490 and Ischemia

ag-490 has been researched along with Ischemia* in 1 studies

Other Studies

1 other study(ies) available for ag-490 and Ischemia

ArticleYear
Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury.
    Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2013, Volume: 19, Issue:10

    Warm ischemia/reperfusion (I/R) is a common clinical problem during liver transplantation and liver resection. Warm ischemia also occurs during trauma and shock. However, there is still no safe and promising strategy for protecting the liver from I/R injury. Signal transducer and activator of transcription 3 (STAT3) is a major immediate response molecule for protecting cell survival. In this study, we first confirmed that a pharmacological STAT3 inhibitor, (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), significantly reduced the survival of HepG2 cells, regardless of the serum condition. Furthermore, we created hepatocyte-specific STAT3-deficient mice with the cyclization recombination-locus of X-over P1 (Cre-LoxP) system to study the mechanisms of STAT3 in liver I/R injury. We found that the alanine aminotransferase level was significantly higher in hepatocyte-specific STAT3-deficient mice versus wild-type (WT) mice in a 70% liver I/R injury model. A histopathological examination showed that hepatocyte-specific STAT3-deficient mice suffered more severe damage than WT mice despite similar numbers of polymorphonuclear neutrophils in the 2 groups. These results indicate that endogenous STAT3 signaling in hepatocytes is required for protection of the liver in vitro and in vivo against warm I/R injury. In conclusion, endogenous STAT3 plays an important role in protecting the liver against I/R injury, and STAT3-targeting therapy could be a therapeutic approach to combating liver I/R injury.

    Topics: Alanine Transaminase; Animals; Cell Proliferation; Cell Survival; Disease Models, Animal; Genotype; Hep G2 Cells; Hepatocytes; Humans; Ischemia; Liver; Liver Transplantation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Phosphorylation; Reperfusion Injury; STAT3 Transcription Factor; Tyrosine; Tyrphostins; Warm Ischemia

2013