Does melanin matter in the dark?

Abstract

In living cells, melanin pigment is formed within melanosomes, which not only protect the cells from autodestruction, but also serve as second messenger organelles regulating important skin functions, with melanocytes acting as primary sensory and regulatory cells of the epidermis. Yet, one can argue that skin melanin, which may negatively affect cellular homeostasis in melanoma, really exerts protective functions. Consequently, the actual functions of melanin and the melanogenic pathway in skin biology remains enigmatic. Yet, the solution of this riddle seems simple - to check the actual influence of natural melanin on skin cells in the dark. Since many interesting hypotheses and theories put forward in this respect did not survive confrontation with the experiment, a leading pigment research group from Naples was brave to "jump off the cliff" by confronting theory with experimental reality. They showed that, in the dark, human hair-derived melanin promotes inflammatory responses in keratinocytes, lowers their viability, promotes oxidative stress, and that pheomelanin does so more strongly than eumelanin. Thus, pheomelanin hardly protects red-haired individuals, even when avoiding the sun. Black hairs do not do much better either, unless they undergo graying.

Keywords: inflammation; keratinocytes; melanocytes; protection; toxicity.

Figure 1

Selected primary pathways of melanin action in the light and in the dark. In the light, melanin produced by melanocytes (M) in melanosomes is transferred (blue arrows) to keratinocytes and other target cells (K) where it mainly protects them from sun (umbrella). This may outweigh harmful effects (thunderbolts) observed for isolated melanins in the dark (predominantly pheomelanin). Internalization of extracellular melanin by keratinocytes is unknown (?). Melanin may act directly or via releasing adsorbed substances, mainly metal ions (Me), affecting intracellular antioxidants (NADPH) and changing the metabolism, or inducing inflammation (ILs, TNFs, etc.). It can be modulated by phototype and influenced by exogenous protectors and antioxidants. Red arrow indicates possibility of acting as signal transducer (messenger) conveying information (i).