Figure 3.

A schematic overview of the potential signaling pathways involved in cytokine-mediated regulation of hypoxia-induced hypoxia-inducible factor-1α (HIF-1α) translocation and activation. Hypoxia and inflammatory signals induce the intracellular accumulation of reactive oxygen species (ROS), which may cause changes in the phosphorylation state of target kinases, thereby mediating a specific regulatory mechanism. The mitochondrion is a potential source for cytokine-unleashed ROS, whose regulation is selectively mediated by antioxidants. ROS-mediated signaling allows HIF-1α protein stabilization, nuclear translocation and transcriptional activation.