Reactive oxygen species and reactive nitrogen species in vitiligo

Abstract

Massive ROS/RNS generation affects the entire epidermal compartment in vitiligo. Oxidative imbalance can also be found in the system. These patients have no increased risk to develop skin cancer despite the absence of pigment. The disease is associated with DNA damage in the epidermis as well as in the system which is effectively repaired by a functioning persistent up-regulated wild type p53 coupled to induction of both short patch and long patch base excision repair as well as enhanced DNA-binding capacity in the presence of H 2 O 2 and ONOO -. Degradation of p53 seems to be prevented by up-regulated p76 MDM2. There is no evidence for increased skin cancer/photodamage and epidermal apoptosis in this disease. Some evidence supports ROS mediated T cell activation and T cell response as well as the possibility of neoantigen formation due to H 2 O 2 /ONOO - -mediated oxidation/nitration of proteins. Considering that normally oxidised proteins and oxidatively-modified biomolecules are cleared by proteasomal/ubiquination degradation, autophagy or lysosomes, it could be possible that H 2 O 2 -mediated oxidation and the presence of ONOO - and its protonated peroxinitrious acid (ONOOH) leads to dysfunction or even deactivation of this important machinery. At this point it is tempting to propose incomplete proteasomal degradation/ubiquination for ineffective clearing of altered proteins leading in turn to the formation of antibodies against melanocytes and other tissues which then can elicitate a cellular immune response in this disease. Moreover, epigenetics becomes of great interest in the scenario. In the light of epidermal and systemic H 2 O 2 accumulation, it is tempting to speculate that environmental (exogenous) and/or systemic (endogenous) trigger factors could be the mechanisms for the hit that increases H 2 O 2 production via NADPH-oxidase in the microenvironment. This could tip the balance and cause the initial loss of constitutive pigment due to generation of hydroxyl radicals (OH •-) from H 2 O 2 via the UV-catalysed Haber-Weiss reaction in susceptible individuals. However, in the subsequent process of the disease, the origin of H 2 O 2 derives from various sources, which could well foster the run mechanism, where H 2 O 2 activates T cell proliferation with consequent activation of T cell clones. Future work is needed to find the true cause of the disease. However, to date translation of the scientific data lead to development of an effective correction/control of the impaired epidermal and systemic redox imbalance via a NB-UVB activated pro-pseudocatalase PC-KUS in association with cessation of the disease and regaining of the skin colour.