Melanocytes as Instigators and Victims of Oxidative Stress

Abstract

Epidermal melanocytes are particularly vulnerable to oxidative stress due to the pro-oxidant state generated during melanin synthesis, and to intrinsic antioxidant defences that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress-driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment.

Melanocytes and Oxidative Stress

“…Exposing melanocytes to UV results in a rapid generation of H 2 O 2 and corresponding decrease in catalase activity [68] and reduced Ho-1 expression [27]. Disregarding the role of UV exposure, there is increasing evidence for the responsibility of oxidative stress in both initiation and progression of melanoma [8], based on the finding that the activating V600E BRAF mutation, commonly expressed in nevi and melanoma, and could be induced by oxidative stress [69]. Melanoma risk was also found to be increased by MC-1R variant alleles [31,70] suggesting that ROS would be a driver of melanomagenesis [71].…”

“…Skin, because of its direct interface with the environment, is the major source of UV-induced ROS for the body. Owing not only to environmental UV-exposure but also to the pro-oxidant state generated during melanogenesis, melanocytes are both 'instigators and victims of oxidative stress [8].…”

“…With regards to dermatology, the role of ROS is more and more highlighted in various diseases such as melanoma [8], acne [9,10] or vitiligo [11].…”

Autoantibodies Profile in Vitiligo

“…Several melanosome glycoproteins have been shown to be antigenic in human. A previous study on antibody responses to a melanocyte autoantigen, TRP-2, found that this autoantigen is immunogenic in human [59]. The TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo and melanoma patients responding to immunotherapy who have induced hypopigmentation [60].…”

High Doses of Ascorbate (Vitamin C): A New Frontier in the Treatment of Intraocular Cancer

“…However, it is quite clear that both uveal and skin melanoma, depend on a dysregulation of the cellular Red-Ox state [112][113][114][115] with an increase in the production of ROS, which represents an indication for prevention with antioxidant and treatment with pro-oxidant molecules, a role which can be fully interpreted by ascorbate, depending on the dose administered.…”