4-Hydroxynonenal-induced apoptosis in rat hepatic stellate cells: mechanistic approach.
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.
de Villiers
Willem J S
WJ
Division of Digestive Diseases, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, USA.
Song
Zhenyuan
Z
Nasser
Munira S
MS
Deaciuc
Ion V
IV
McClain
Craig J
CJ
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
D000447:Aldehydes; C027576:4-hydroxy-2-nonenal