the human sirtuin It is most closely related to Sir2

Socs3 h KO mice show marked enhancement of hepatocyte DNA replication, as demonstrated by increased BrdU incorporation, Nuclear hepatocyte BrdU labeling in Socs3 h KO mice is sig nificantly higher than in control littermates from 32 to 48 h after PH, and is 160% higher at the peak of DNA reproduction tion between Bromosporine 36 and 40 h after PH. Furthermore, the number of hepatocyte mitoses is 85 and 89% higher in Socs3 h KO mice than that of controls at 48 and 72 h, respectively, As a result of the increased hepatocyte replication in Socs3 h KO mice, these animals restore their liver weights after PH 2 d earlier than do controls, To help expand demonstrate negative regulation by SOCS3 of the progression of hepatocytes through the cell cycle within the regenerating liver, we performed immunoblotting for the cell cycle proteins cy clin An and p107, which are regarded as up regulated during liver regeneration, Lysates farmed between 24 We thus performed Northern blotting for Socs3 on RNA isolated from Socs3 h KO and control littermates at different times after PH. We identified virtu ally no induction of Socs3 after PH in the KO mice at the Endosymbiotic theory situations reviewed and, likewise, did not discover a compensatory up regulation of Socs1, In summary, the information presented in this section clearly demonstrate that SOCS3 deficit increases hepatocyte replication and accel erates liver regeneration after PH. Activation of STAT3 and extracellular signal regulated kinase signaling pathways in Socs3 m KO mice after PH After PH, Il6 is produced by Kupffer cells on the surface of hepato cytes and subse quently binds its specific receptor. Receptor binding activates JAK to phosphorylate and activate STAT3, which in PF-04620110 turn dimerizes and translocates to the nucleus. As we have earlier demonstrated that Socs3 term,after PH is essentially dependent on the IL 6 STAT3 signaling pathway, we examined the activation of this pathway during liver regeneration in Socs3 h KO mice. Serum IL 6 levels were determined by ELISA from 30 min to 12 h after PH and don't significantly differ between Socs3 h KO and control littermates, This effect isn't unexpected, as the generation of IL 6 by NPCs wouldn't be al tered by SOCS3 deficit in hepatocytes.