What's the use of generating melanin?

Abstract

The CONTROVERSIES featured in the August 1998 issue of Exp Dermatol have discussed the controls of melanogenesis (Schallreuter et al., Exp Dermatol 7: 143-150, 1998). Now, we explore the biological functions of the endproduct of melanogenesis, the various melanin biopolymers. As delineated in the subsequent contributions, melanins are func- Viewpoint 1Melanins are found in highly oxidizing situations where significant concentrations of oxygen radicals are generated. Such reactive oxygen species (ROS) are produced by UV-light in the skin and eye, by sound and ultrasound in the inner ear, and in the highly oxidizing conditions of catecholaminergic neurons in the brain. The role of the melanins as oxygen radical trapping polymers, UV-light filters, polymeric buffers for transition metals, calcium and catecholamines will be considered in this viewpoint. For the Dermatologist it is of special interest to understand those factors that control melanogenesis in the skin and hair (3). In this context the pterins, alpha melanocyte stimulating hormone (a-MSH) and calcium appear to be central in the regulation of both melanin content and composition in melanocytes. There is accumulating evidence that the evolution of melanogenesis in human melanocytes is primarily antioxidant in character and is designed to protect these pigment cells from the cytotoxicity of ROS. However, the subtle link between calcium homeostasis and melanogenesis suggests that natural skin colours in the human population may have evolved secondarily as a consequence of salt balance/dehydration fac-153 tionally much more complex and fascinating than their evident colour-awarding and UV-light-filtering properties suggest, and dermatologists and pigment biologists alike have yet to discover and define the full range of biologically relevant melanin functions in health and disease.tors as primates adapted to extreme differences in local climates. It is tempting to speculate that skin colour emerged as a side effect through Darwinian natural selection principles in tropical versus temperate climates.There is increasing evidence that melanogenesis represents a major antioxidant defence mechanism in melanocytes. Melanocytes in the human epidermis (in vivo) or in cell cultures (in vitro) have been shown to be much more sensitive to the cytotoxicity of ROS than keratinocytes (17, 27). This concept is especially well-documented by the cytotoxicity of hydrogen peroxide (H 2 O 2 ) to melanocytes both (in vivo) and (in vitro) (6,14,15,17). Consequently, melanocytes have evolved an effective strategy to deal with the removal of superoxide anion radicals (O 2 ª ) before these radical anions disproportionate to H 2 O 2 .The preferential utilization of O 2 ª compared to dioxygen (O 2 ) is quite a common event in the skin. The enzymes tyrosinase, proline hydroxylase and indoleamine 2,3 dioxygenase selectively utilize O 2 ª as the preferred substrate over O 2 for the formation of dopaquinone, hydroxyproline residues in collagen, and kynurenic acid respectively (2, 20, 21,...

Melanocytes and Skin Immunity

“…Melanin may also have an immunoregulatory role. It has been found to have immunomodulatory activities through inhibition of proinflammatory cytokine production by T lymphocytes, monocytes, fibroblasts, and endothelial cells (Wood et al, 1999;Mohagheghpour et al, 2000).…”

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

“…The phenotypic expression of this is generally classified according to the clinical Fitzpatrick skin types 1 through 6 and emphasizes the inverse relationship between the degree of pigmentation and solar damage to the skin, including photocarcinogenesis. The functions of melanin pigments include protection from UV light, control of vitamin D3 synthesis, and local thermoregulation [1,15,16]. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, autocrine, paracrine, or intracrine fashion [1].…”

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

“…10,11 The major role of cutaneous melanin is protection against the harmful actions of solar radiation, by acting as a filter against ultraviolet radiation (UVR), preventing its penetration and genotoxicity (formation of UV-induced DNA dimmers). [11][12][13][14][15][16] Melanin also neutralizes reactive oxygen species (ROS) generated mostly by UVA, through its antioxidative and free-radical scavenging actions. 13,16,17 Overall, melanin protects against epidermal carcinogenesis or melanomagenesis.…”

“…[11][12][13][14][15][16] Melanin also neutralizes reactive oxygen species (ROS) generated mostly by UVA, through its antioxidative and free-radical scavenging actions. 13,16,17 Overall, melanin protects against epidermal carcinogenesis or melanomagenesis. 11,12,14,16 Nevertheless, the same positive capacity of melanin to scavenge free radical and ROS becomes undesirable in the response of melanoma to radio-, photo-or chemotherapy 11,16,[18][19][20] ; furthermore, the pro-oxidant properties of melanin can, in certain conditions, stimulate melanoma progression.…”