Figure 2.

Schematic illustration of how copper promotes angiogenesis. The pro-angiogenetic signaling pathway affected by copper is the regulation of HIF-1α degradation, where copper inhibits the hydroxylation of prolyl residues to maintain the intracellular concentration of active HIF-1α. Copper also influences the combination between HIF-1 transcriptional complex and HRE sites. It was also speculated that copper also directly actives HIF-1α via downregulating the expression of GSK-3β. Abbreviations: HIF: hypoxia-inducible facto; PHD: prolyl hydroxylase domain-containing protein; VHF: von Hippel–Lindau protein; GSK-3β: glycogen synthase kinase-3β; CBP: CREB-binding protein; the red straight line with arrow means activation; the green straight line with straight-arrow means inhibition; the green truncated line with straight-arrow means inhibition under speculation.