title: 4-Hydroxynonenal-induced apoptosis in rat hepatic stellate cells: mechanistic approach.
abstract: OBJECTIVE
  Although lipid peroxidation products act as apoptotic signals for several cell types, including hepatic stellate cells, the underlying mechanisms are not well understood. In this study we determined if: (i) 4-hydroxy-2,3-nonenal (HNE) induces apoptosis in two rat stellate cell lines, HSC-T6 and CFSC-2G; and (ii) if apoptosis is regulated at the transcriptional and/or translational level.
  
  
  METHODS
  HSC-T6 and CFSC-2G cells were treated with HNE and total RNA and protein extracted. mRNA and protein expression levels of pro- and antiapoptotic factors were determined. The effects of HNE on activation, morphology and cell death by apoptosis were also studied.
  
  
  RESULTS
  HNE caused dose-dependent apoptosis in both HSC-T6 and CFSC-2G cell lines. Apoptosis in HSC-T6 cells was associated with increased mRNA expression of the pro-apoptotic adaptors/regulators FasR, FasL, Bax, and caspases-2 and -3. In contrast, CFSC-2G cells showed no changes in FasR, Bax and caspase-3 mRNA levels. Caspase-3 activity was elevated in T6 but not in 2G cells. Changes in protein expression generally paralleled the mRNA findings.
  
  
  CONCLUSIONS
  HNE-induced apoptosis of both CFSC-2G and HSC-T6 rat hepatic stellate cells is associated with changes in mRNA and protein expression of several apoptotic adaptors/regulators. The underlying mechanism for HNE-induced apoptosis may involve both transcriptional and translational regulatory steps.
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, USA.
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Song
authors.forename: Munira S
authors.initials: MS
authors.lastname: Nasser
authors.forename: Ion V
authors.initials: IV
authors.lastname: Deaciuc
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology* / Q000187:drug effects*; D051381:Rats
chemical_list: D000447:Aldehydes; C027576:4-hydroxy-2-nonenal