Modulation of paraoxonase-2 in human dermal fibroblasts by UVA-induced oxidative stress: A new potential marker of skin photodamage

Abstract

Paraoxonase-2 (PON2) is an intracellular protein, that exerts a protective role against cell oxidative stress and apoptosis. Genetic and environmental factors (i.e. dietary factors, cigarette smoke, drugs) are able to modulate cellular PON2 levels. The effect of ultraviolet A radiation (UVA), the oxidizing component of sunlight, on PON2 in human dermal fibroblasts (HuDe) has not been previously explored. Excessive UVA radiation is known to cause direct and indirect skin damage by influencing intracellular signalling pathways through oxidative stress mediated by reactive oxygen species (ROS) that modulate the expression of downstream genes involved in different processes, e.g. skin photoaging and cancer. The aim of this study was, therefore, to investigate the modulation of PON2 in terms of protein expression and enzyme activity in HuDe exposed to UVA (270 kJ/m2). Our results show that PON2 is up-regulated immediately after UVA exposure and that its levels and activity decrease in the post-exposure phase, in a time-dependent manner (2–24 h). The trend in PON2 levels mirror the time-course study of UVA-induced ROS. To confirm this, experiments were also performed in the presence of a SPF30 sunscreen used as shielding agent to revert modulation of PON2 at 0 and 2 h post-UVA exposure where other markers of photo-oxidative stress were also examined (NF-KB, γH2AX, advanced glycation end products). Overall, our results show that the upregulation of PON2 might be related to the increase in intracellular ROS and may play an important role in mitigation of UVA-mediated damage and in the prevention of the consequences of UV exposure, thus representing a new marker of early-response to UVA-induced damage in skin fibroblasts.