Depletion of β-arrestin 2 protects against CCl4-induced liver injury in mice

Acute liver injury can be caused by oxidative stress within a short period and is a common pathway to many liver diseases. The liver is vulnerable to reactive oxygen species (ROS) and free radical-mediated disorders. beta-arresting was initially discovered to be a negative regulator of G protein-coupled receptor signaling. Recently, beta-arresting has been found to act as a multifunctional adaptor protein and play new roles in regulating intracellular signaling networks. However, the role of beta-arresting in the pathogenesis of acute liver injury is unclear. In this study, we hypothesize that beta-arresting regulates acute liver injury via modulation of oxidative stress. beta-arresting knockout mice were used to investigate the impacts of beta-arrestin2 on carbon tetrachloride (CCl4)-induced acute liver injury and oxidative stress. Results here suggested that beta-arresting deficiency decreased serum activities of aminotransferase and alleviated liver injury induced by CCl4 injection as compared with wildtype mice. beta-arresting knockout mice exhibited stronger tolerance in oxidative stress compared with wild-type mice, which was demonstrated by decreased ROS level and increased superoxide dismutase (SOD) and glutathione (GSH) in the liver. Furthermore, beta-arresting deficiency significantly inhibited NOX4 (a major source of ROS) expression and the activation of the extracellular regulated kinase (ERK) and, c-Jun NH2-terminal kinase (JNK) pathways. These results suggest that beta-arresting deficiency protects against CCl4-induced acute liver injury through attenuating oxidative damage and decreased ERK and JNK phosphorylation. (C) 2019 Elsevier Inc. All rights reserved.