Caspase-12 expression and activation in the pathogenesis of acute hepatic failure induced by lipopolysaccharide and D-galactosamine / 中华肝脏病杂志
Chinese Journal of Hepatology
;
(12): 685-688, 2005.
Article
in Chinese
| WPRIM
| ID: wpr-276387
ABSTRACT
<p><b>OBJECTIVE</b>To study the role of caspase-12 expression on hepatocyte apoptosis in an experimental model of acute hepatic failure (AHF).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
RNA, Messenger
/
Random Allocation
/
Lipopolysaccharides
/
Liver Failure, Acute
/
Apoptosis
/
Hepatocytes
/
Caspase 12
/
Galactosamine
/
Genetics
Type of study:
Etiology study
Limits:
Animals
Language:
Chinese
Journal:
Chinese Journal of Hepatology
Year:
2005
Type:
Article
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