The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been demonstrated to increase p53 levels in skin, which would presumably allow for repair of cells with damaged DNA, or apoptosis of cells with irreparably damaged DNA. Previous studies have also shown that p53 reduces intracellular ROS. Furthermore, 1,25D has been shown to induce metallothioneins, which are potent free radical scavengers. In addition to these protective effects, 1,25D has been demonstrated to inhibit stress-activated c-Jun N-terminal kinases following UV exposure, and to increase levels of the stress-induced protein heme oxygenase-1 in a model of oxidative stress. Herein, we discuss the protective effects of 1,25D and analogs in the context of UV, oxidative stress and skin cancer.
Keywords: 1,25-dihydroxyvitamin D3 (1,25D); DNA damage; Vitamin D; c-Jun N-terminal kinases (JNK); metallothionein (MT); oxidative stress; p53; reactive oxygen species (ROS).