ROS and AGE feedback loop through NOX. ROS and AGEs can form a feedback loop, initiated by glucose and glycolytic intermediates forming AGEs, which activate the NADPH oxidase complex (NOX complex) through PKC and AA. PKC, activated by AGEs, phosphorylates the P47phox subunit of NOX, allowing for assembly of the complex. AGEs then shuttle AA to P47phox, increasing the activity of the complex. Excess ROS created by this complex cause DNA damage in the nucleus that leads to a buildup of glycolytic intermediates upstream that then perpetuate the cycle by their conversion into AGEs. AA, arachidonic acid; AGEs, advanced glycolytic end products; NOX, NADPH oxidase; PKC, protein kinase C; ROS, reactive oxidative species. Color images are available online.