Inhibitive mechanisms of Pim-3 affecting fulminant hepatic apoptosis.
10.3760/cma.j.issn.1007-3418.2012.09.010
- Author:
Liang-ming LIU
1
;
Shui-lin SUN
;
Chang-gen YE
;
Dong-yu LIANG
;
Liang ZHAO
;
Fang-ping YU
;
Ji-xiang ZHANG
Author Information
1. Department of Liver Diseases, Songjiang Hospital Affiliated to the First People's Hospital, Shanghai Jiaotong University, China. liuliangming@hotmail.com
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
Caspase 3;
metabolism;
Liver;
metabolism;
pathology;
Liver Failure;
metabolism;
pathology;
Male;
Protein-Serine-Threonine Kinases;
genetics;
Rats;
Rats, Wistar
- From:
Chinese Journal of Hepatology
2012;20(9):688-692
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the mechanisms of serine/threonine kinase Pim-3 inhibition of fulminant hepatic apoptosis. Thirty-two rats were randomly divided into four groups (n = 8 each): normal controls (A); pretreatment with Ringer's solution (B), vector plasmid (C), or Pim-3 recombinant plasmid (D) by hydrodynamics-based procedure followed by intraperitoneal injections of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) after one day. At 8 h after the LPS/D-GalN injections, liver tissues were collected from all groups of mice and analyzed for cell apoptosis by detecting caspase-3 activity (measured in relative fluorescence units, RFU). Changes in expression of relevant genes were determined by RT-PCR and Western blotting. Caspase-3 activity was induced in response to LPS/D-GalN injection. Pim-3-pretreated rats showed a lower level of caspase-3 activity than the Ringer's-pretreated or vector plasmid-pretreated rats [(141.7+/-13.7)RFU vs. (508.1+/-32.0) or (493.5+/-33.1) RFU; all P less than 0.01]. High expressions of the liver injury marker gene, iNOS, and the apoptosis-induced genes, p53 and Bax, were found after LPS/D-GalN challenge, and were suppressed by exogenous Pim-3 gene injection. In addition, exogenous Pim-3 gene injection induced high expression of the liver anti-apoptosis protein, Bcl-2, but had no effect on Bax protein expression. The Pim-3 gene can block fulminant hepatic apoptosis by affecting the expression of the iNOS liver injury gene and the p53, Bax and Bcl-2 apoptosis-related genes.
