Adaptive antioxidant response and photoaging

Abstract

As the skin is always in contact with oxygen and is increasingly exposed to environmental and artificial ultraviolet (UV) irradiation the risk of photooxidative damage induced by reactive oxygen species – finally leading to phototoxicity, photoaging and skin cancer – has increased substantially.The term reactive oxygen species (ROS) includes oxygen centered radicals like the superoxide anion radical and the hydroxyl radical, but also non‐radical species such as hydrogen peroxide and singlet oxygen – all being produced in skin upon UV irradiation. In response to the attack of reactive oxygen species the skin has developed a complex antioxidant defense system including enzymatic and non‐enzymatic antioxidants. As a first line of the enzymatic antioxidative defense, superoxide dismutases reduce superoxide anion radicals to hydrogen peroxide which subsequently is detoxified to water by catalase and glutathione peroxidases.We were interested whether the antioxidant enzymes manganese superoxide dismutase (SOD2) and glutathion peroxidase (GPx1) are inducible upon UV irradiation and whether repetitive UV exposure, as practiced for the light‐hardening during phototherapy of photodermatoses, can even enhance the adaptive antioxidant response. To address this question skin fibroblasts and keratinocytes were exposed in vitro to single and repetitive UV low dose irradiation in different time intervals and afterwords challenged by high dose irradiation. The antioxidant response was measured in terms of steady state mRNA levels and activity changes of SOD2 or GPx1 as well as of the viability after challenge with high dose UV‐irradiation.Interstingly, only UVA but not UVB irradiation was able to induce the mRNA steady state levels and the activity of SOD2 in fibroblasts. However, fibroblasts incubated with the supernatants from UVB‐irradiated epidermal cells responded with an increase in SOD2. This increase on mRNA and activity levels was mediated by paracrine acting secreted factors produced by the keratinocytes. If fibroblasts were exposed repetitively to sublethal UVA doses the further up‐regulation of SOD2 correlated with the protection against high UV doses. Importantly, SOD2 basal levels of protein content and activity substantially differed within cultivated cells and skin biopsies from different individuals. These results provide evidence for an adaptive antioxidative UV response of the skin. Interindividual differences might account for differences in the susceptibility to develop photodermatologic disorders related to photosensitivity, photoaging, and skin cancer.