Caspase-12 expression and activation in the pathogenesis of acute hepatic failure induced by lipopolysaccharide and D-galactosamine.
- Author:
Hui-juan ZHOU
1
;
Qing XIE
;
Shan JIANG
;
Guang-ming LI
;
Xia-qiu ZHOU
;
Hai-fang LIU
;
Hong YU
;
Qing GUO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Caspase 12; biosynthesis; genetics; Galactosamine; Hepatocytes; pathology; Lipopolysaccharides; Liver Failure, Acute; chemically induced; metabolism; Male; Mice; Mice, Inbred BALB C; RNA, Messenger; biosynthesis; genetics; Random Allocation
- From: Chinese Journal of Hepatology 2005;13(9):685-688
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the role of caspase-12 expression on hepatocyte apoptosis in an experimental model of acute hepatic failure (AHF).
METHODSA 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.
RESULTSCaspase-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.
CONCLUSIONHepatocyte 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.