Figure 1.

Regulation of HIF-1α under hypoxic conditions. Under normoxia, HIF-1α is inhibited by PHD and FIH and cannot bind to HIF-1β. Hypoxia binds to HIF-1β and recruits p300 or CBP to respond adaptively to hypoxia, inducing the expression of many genes such as GLUT1 and HK2, thus promoting glycolysis to produce energy and also stimulating angiogenesis and DNA damage. Intracellular cAMP levels increase after sustained hypoxia, and cAMP and senescence act through signaling pathways such as AMPK-mTOR, ultimately producing SASP to play a physiological role. PHD—prolyl hydroxylase domain; FIH—factor inhibiting HIF-1; pVHL—VHL (Von Hippel–Lindau) tumor suppressor protein; SASP—senescence-associated secretory phenotype; ROS—reactive oxide species; TNF-α—tumor necrosis factor-α; VEGF—vascular endothelial growth factor; CCL—chemokine; HRE—hypoxia response element; GLUT1—glucose transporter type 1; HK-2—hexokinase 2; iNOS—inducible nitric oxide synthase.