Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture.

Hyaluronan (HA) is produced by keratinocytes in human skin organ culture, and degraded locally in epidermis by an unknown metabolic route. The present work tested whether reactive oxygen species (ROS), spontaneously produced in the tissue, could contribute to HA catabolism in epidermis. Epidermal HA was endogenously labeled with 3H-glucosamine for 24 h, then chased for 24 h in the presence of superoxide dismutase (SOD) and catalase to reduce the concentration of ROS. In control cultures, 35% of labeled HA was degraded during the 24 h chase while the corresponding figures in the presence of SOD and catalase were 19% and 23%, respectively (p < 0.05). Methionine, a quencher of hypochlorous acid, did not significantly inhibit the degradation. In additional experiments, the iron and copper chelator Detapac was even more effective, reducing the degradation to 8-9%, and suggesting that the ROS responsible for the degradation were produced in the Fenton reaction. Dermal HA, and proteoglycans in both epidermis and dermis were not influenced by the treatments, indicating that the inhibition by SOD, catalase and Detapac on epidermal HA catabolism was specific. It is suggested that endogenous ROS is involved in the catabolism human epidermal HA.