This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, Y.-D. Articles by Huang, W. Search for Related Content PubMed PubMed Citation Articles by Wang, Y.-D. Articles by Huang, W.

Farnesoid X Receptor Protects Liver Cells from Apoptosis Induced by Serum Deprivation in Vitro and Fasting in Vivo

Department of Gene Regulation and Drug Discovery, Beckman Research Institute of City of Hope National Medical Center, Duarte, California 91010

Address all correspondence and requests for reprints to: Wendong Huang, Ph.D., Department of Gene Regulation and Drug Discovery, Beckman Research Institute of City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California 91010. E-mail: whuang{at}coh.org.

The farnesoid X receptor (FXR) is a key metabolic regulator in the liver by maintaining the homeostasis of liver metabolites. Recent findings suggest that FXR may have a much broader function in liver physiology and pathology. In the present work, we identify a novel role of FXR in protecting liver cell from apoptosis induced by nutritional withdrawal including serum deprivation in vitro or starvation in vivo. Two FXR ligands, chenodeoxycholic acid (CDCA) and GW4064, rescued HepG2 cells from serum deprivation-induced apoptosis in a dose-dependent manner. This effect of FXR on apoptotic suppression was compromised when FXR was knocked down by short interfering RNA. Similarly, the effects of both CDCA and GW4064 were abolished after inhibition of the MAPK pathway by a specific inhibitor of MAPK kinase 1/2. Immunoblotting results indicated that FXR activation by CDCA and GW4064 induced ERK1/2 phosphorylation, which was attenuated by serum deprivation. In vivo, FXR^–/– mice exhibited an exacerbated liver apoptosis and lower levels of phosphorylated-ERK1/2 compared to wild-type mice after starvation. In conclusion, our results suggest a novel role of FXR in modulating liver cell apoptosis.

NURSA Molecule Pages Link:

Nuclear Receptors:   FXRα

Ligands:   GW4064