Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance.

ABSTRACT: The liver is frequently challenged by surgery-induced metabolic overload, viruses or toxins, which induce the formation of reactive oxygen species. To determine the effect of oxidative stress on liver regeneration and to identify the underlying signaling pathways, we studied liver repair in mice lacking the Nrf2 transcription factor. In these animals, expression of several cytoprotective enzymes was reduced in hepatocytes, resulting in oxidative stress. After partial hepatectomy, liver regeneration was significantly delayed. Using in vitro and in vivo studies, we identified oxidative stress-mediated insulin/insulin-like growth factor resistance as an underlying mechanism. This deficiency impaired the activation of p38 mitogen-activated kinase, Akt kinase and downstream targets after hepate

SUBMITTER: Beyer TA 

PROVIDER: S-EPMC2206132 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature