Abstract 13113: Identification of Novel Copper-dependent Wound Repair Mechanism: Role of Copper Transport Protein Antioxidant 1

Copper (Cu) facilitates wound healing and angiogenesis with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins, including cytosolic Cu-chaperone Atox1, which is required for activation of secretory Cu enzymes. Atox1 also functions as a Cu-dependent transcription factor, but its role in wound healing is unknown. Using mouse skin puncture model, here we show that Atox1 protein (8-fold) and Cu-level (by X-ray Fluorescence Microscopy; 2.5-fold) were increased in wounding tissue in wild type (WT) mice at day 7 when Atox1 was localized in nucleus of dermal endothelial cells (ECs) as well as cytosol of epidermal cells, granulation tissue. Furthermore, topical Cu treatment enhanced (20% vs PBS), but specific Cu chelator BCS reduced wound repair in WT mice. Importantly, Atox1 knockout (KO) mice showed abolished topical Cu-induced wound repair or impaired endogenous wound healing vs. WT mice, which was associated with decreased angiogenesis (CD31+, 45% ), proliferation (BrdU+, 60%), ROS-pr...