| First Author | Wang C | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 22 | Pages | 4492-503 |
| PubMed ID | 24043304 | Mgi Jnum | J:206095 |
| Mgi Id | MGI:5547883 | Doi | 10.1128/MCB.00160-13 |
| Citation | Wang C, et al. (2013) Poly(ADP-ribose) polymerase 1 promotes oxidative-stress-induced liver cell death via suppressing farnesoid X receptor alpha. Mol Cell Biol 33(22):4492-503 |
| abstractText | Farnesoid X receptor alpha (FXR) is highly expressed in the liver and regulates the expression of various genes involved in liver repair. In this study, we demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP1) promoted hepatic cell death by inhibiting the expression of FXR-dependent hepatoprotective genes. PARP1 could bind to and poly(ADP-ribosyl)ate FXR. Poly(ADP-ribosyl)ation dissociated FXR from the FXR response element (FXRE), present in the promoters of target genes, and suppressed FXR-mediated gene transcription. Moreover, treatment with a FXR agonist attenuated poly(ADP-ribosyl)ation of FXR and promoted FXR-dependent gene expression. We further established the CCl4-induced acute liver injury model in wild-type and FXR-knockout mice and identified an essential role of FXR poly(ADP-ribosyl)ation in CCl4-induced liver injury. Thus, our results identified poly(ADP-ribosyl)ation of FXR by PARP1 as a key step in oxidative-stress-induced hepatic cell death. The molecular association between PARP1 and FXR provides new insight into the mechanism, suggesting that inhibition of PARP1 could prevent liver injury. |
