Figure 4

Effects of TrkA and p75 NTR blocker treatments on bile duct ligation (BDL)-induced PARP cleavage and apoptosis of parenchymal hepatocytes. The mice receiving BDL surgery were intraperitoneally administered with either recombinant NGF (n=6) twice weekly or PBS (n=6), GW441756 (GW; n=6), DMSO (n=3) or PD90780 (PD; n=6) daily. After 2 weeks of treatment, pooled liver extracts of each group were subjected to western blotting to detect both propeptides and cleaved forms of caspase-3 and PARP (a). Density analysis of the activation of caspase-3 (b) and PARP (c), shown as the ratios of cleavage to propeptide content, followed by normalization to negative control (NC) levels. IHC staining for active PARP peptides (d) and labeling index (e) quantitatively demonstrated that PD90780 administration potentiated the increase of PARP activation in BDL-treated mouse livers. (f) Representative microphotographs of TUNEL staining showing the apoptotic events in mouse liver sections. Scale bars=50 μm. (g) Analysis of TUNEL-positive parenchymal cells indicated that recombinant NGF administration exerted a protective effect, whereas treatment with a p75NTR antagonist, PD90780, increased apoptotic cell death in BDL-induced cholestatic injured livers. All data are shown as the mean±s.e.m. *P<0.05 between indicated groups. ND, not detectable. NS, not significant.