The Landscape of Interactions between Hypoxia-Inducible Factors and Reactive Oxygen Species in the Gastrointestinal Tract

Figure 3

Interactions between HIF-1α and ROS in the gastrointestinal tract. ROS induce the expression of HIF-1α by activating ERK, NF-κB, and PI3K/Akt/mTOR signaling pathways. Further, ROS regulate the stability and activity of HIF-1α by targeting VHL, PHD, and ARNT. In return, HIF-1α suppresses ROS generation by inhibiting mitochondrial OXHPS. HIF-1α: hypoxia-inducible transcription factor-1α; ROS: reactive oxygen species; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; VHL: von Hippel-Lindau; PHD: prolyl 4-hydroxylase; ARNT: aryl hydrocarbon receptor nuclear translocator.