FIG. 6.

Schematic of RAGE/ NF-κB regulation of oxidative injury. The mitochondrial respiratory chain is the major intracellular source of reactive oxygen species (ROS). Radiation therapy and some forms of chemotherapy rely on ROS toxicity to eradicate tumor cells. However, ROS such as H₂O₂ increase activity of NF-κB and subsequently result in RAGE overexpression. This RAGE upregulation protects pancreatic tumor cells against oxidative injury by increasing programmed cell survival (autophagy) and decreasing programmed cell death (apoptosis). Furthermore, RAGE also sustains NF-κB activation by positive regulation in response to oxidative injury.