Suppression of autophagy in rat liver at late stage of polymicrobial sepsis.
Shock
; 35(5): 506-11, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-21263383
ABSTRACT
Sepsis develops as a result of the host response to infection, and its mortality rate in ICU remains high. Severe inflammation usually causes overproductions of proinflammatory cytokines, i.e., TNF-α and reactive oxygen species, which lead to mitochondrial damage and energetic depletion. Autophagy is a survival mechanism for eukaryote to recycle intracellular nutrients and maintain energy homeostasis. We hypothesize that autophagy plays a beneficial role in the pathogenesis of organ failure during sepsis. A rat model of cecal ligation and puncture (CLP) that simulate peritonitis-induced sepsis was used, and indicators for liver dysfunction, serum glutamic oxaloacetic, serum glutamic pyruvic, alkaline phosphatase, and bilirubin were measured. Levels of LC3-II and LC3 aggregation were quantified by Western blot analysis and by immunohistochemistry, respectively. The tissue localization of autophagy was identified by immunohistochemistry and transmission electron microscopy. Our results showed that (a) increase in LC3-II level in liver tissue occurs at 3 h, peaks at 6 h, and then surprisingly declines quickly until 18 h after CLP (CLP18h); (b) significant hepatic dysfunction was observed at CLP18h; (c) ratio of LC3 aggregation is significantly higher in hepatocytes than in Kupffer cells, and (d) loss of Atg7, an essential gene for autophagosome formation, exaggerates the TNF-α-induced cell death, depletion of ATP, and decrease of albumin production in hepatocytes. These results indicate that autophagy occurs transiently in hepatocytes at early stage, and the decline in autophagy at late stage may contribute to the functional failure in liver during polymicrobial sepsis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Sepsis
/
Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Shock
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Taiwán