title: [Inhibitive mechanisms of Pim-3 affecting fulminant hepatic apoptosis].
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.
authors.affiliation: Department of Liver Diseases, Songjiang Hospital Affiliated to the First People's Hospital, Shanghai Jiaotong University, China. liuliangming@hotmail.com
authors.forename: Liang-ming
authors.initials: LM
authors.lastname: Liu
authors.forename: Shui-lin
authors.initials: SL
authors.lastname: Sun
authors.forename: Chang-gen
authors.initials: CG
authors.lastname: Ye
authors.forename: Dong-yu
authors.initials: DY
authors.lastname: Liang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Fang-ping
authors.initials: FP
authors.lastname: Yu
authors.forename: Ji-xiang
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D017093:Liver Failure / Q000378:metabolism / Q000473:pathology*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C113398:Pim3 protein, rat; D017346:Protein Serine-Threonine Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3