[Caspase-12 expression and activation in the pathogenesis of acute hepatic failure induced by lipopolysaccharide and D-galactosamine].
Zhonghua Gan Zang Bing Za Zhi
; 13(9): 685-8, 2005 Sep.
Article
em Zh
| MEDLINE
| ID: mdl-16174460
ABSTRACT
OBJECTIVE:
To study the role of caspase-12 expression on hepatocyte apoptosis in an experimental model of acute hepatic failure (AHF).METHODS:
A mouse experimental model of AHF was developed by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Hepatocyte apoptosis was examined by DNA agarose gel and liver pathology. Caspase-12 mRNA expression in liver was detected by reverse transcriptase PCR (RT-PCR) method. The expression of caspase-12, GRP78 proteins in livers was determined by Western blot.RESULTS:
Caspase-12 mRNA expression in the livers increased significantly from 5 to 7 hours after administration of LPS and D-Gal. Typical manifestation of hepatocyte apoptosis appeared at 5 hours after the drug administration. After 5 hours the level of serum ALT and AST were remarkably increased, and they reached the peak at 7 hours. The expression of procaspase-12 protein decreased obviously at 7 hours. Seven hours after the drug administration, hepatocyte apoptosis and necrosis both started. The marker of endoplasmic reticulum (ER) stress, Bip/GRP78 was activated during the development of hepatocyte apoptosis. The level of Bip/GRP78 protein was gradually increased at 5 hours after the drug induction.CONCLUSION:
Hepatocyte apoptosis plays an important role in the pathogenesis of AHF. Caspase-12 induced ER stress involves in hepatocyte apoptosis. It suggests that inhibition of caspase-12 activation might be a potential strategy in the treatment of AHF in the future.
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Base de dados:
MEDLINE
Assunto principal:
Falência Hepática Aguda
/
Caspase 12
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2005
Tipo de documento:
Article