Activation of NF-κB by ischemia/reperfnsion in rat liver

We reported that xanthine oxidase(XOD)-derived reactive oxygen species(ROS) was generated during ischemia but not reperfusion. We also reported the I/R-induced apoptosis in liver. On the other hand, NF-κB is a transcription factor that is activated by a various stimulants including cytokines and ROS. NF-κB also contributes to a regulation of apoptosis. In the present study, we investigated that whether NF-κB was activated by I/R in rat liver, and how NF-κB contributed to I/R injury in liver. Male Wistar rats weighing about 300g were used. The portal vein and the hepatic artery to three cephalad lobes were clamped for 1h following reperfusion up to 24h. Activation of NF-κB was determined by Western blot analysis. Western blot analysis of nuclear extracts prepared from ischemic liver lobes was performed using anti-NF-κB p65 antibodies. Levels of NF-κB increased at 1h after ischemia and 6h after reperfusion. The activation of NF-κB at 1h after ischemia may be elicited by XOD-derived ROS. However, the mechanism of activation at 6h after reperfusion remaines unclear. It has been shown that hepatic I/R induced the release of tumor necrosis factor α(TNFα), and NF-κB was activated by TNFα. Therefore, TNFα may contribute to the activation of NF-κB at 6h after reperfusion. In conclusion, these results suggest that NF-κB may contribute to the regulation of apoptosis on I/R injury in liver.