Figure 2.

Summary of oxidative stress triggers and HO-1 related cellular responses. BV: biliverdin, BR: bilirubin; otherwise abbreviations are as defined in the text. Oxidative stresses trigger ROS which in turn trigger the MAPK pathway as well as HO-1 via MAPK dependent and independent mechanisms. MAPK further signals through STAT3 to upregulate HO-1 transcription. HO-1 produces free iron which is sequestered into ferritin, biliverdin which is converted into bilirubin, and CO which is stable and diffuses readily. CO production further increases HO-1 levels. In addition, CO influences multiple other signaling pathways to decrease apoptosis and inflammation.