MITF and UV responses in skin: From pigmentation to addiction

Abstract

Ultraviolet radiation (UVR) has numerous effects on skin, including DNA damage, tanning, vitamin D synthesis, carcinogenesis, and immunomodulation. Keratinocytes containing damaged DNA secrete both α-melanocyte-stimulating hormone (α-MSH), which stimulates pigment production by melanocytes, and the opioid β-endorphin, which can trigger addiction-like responses to UVR. The pigmentation (tanning) response is an adaptation that provides some delayed protection against further DNA damage and carcinogenesis, while the opioid response may be an evolutionary adaptation for promoting sun-seeking behavior to prevent vitamin D deficiency. Here, we review the pigmentation response to UVR, driven by melanocytic microphthalmia-associated transcription factor (MITF), and evidence for UVR-induced melanomagenesis and addiction. We also discuss potential applications of a novel approach to generate protective pigmentation in the absence of UVR (sunless tanning) using a topical small-molecule inhibitor of the salt-inducible kinase (SIK) family.

Oxidative Stress and Genotoxicity in Melanoma Induction: Impact on Repair Rather Than Formation of DNA Damage?

“…The respective amounts of pheo-and eumelanin depend on the efficiency of the dark melanin pathway. In that respect, the melanocortin-1 receptor (MC1R) plays a major role since its activation triggers the biochemical activities at the origin of protecting eumelanin (26)(27)(28). In variants of this receptor protein leading to a slow biosynthesis of eumelanin, most DOPA-Q is used for the production of cysteinyl-DOPA.…”

Exploring the Applications of the Photoprotective Properties of Anthocyanins in Biological Systems

“…Another relevant feature and cosmetic concern associated with photoaging is the manifestation of skin hyperpigmentation. Melanin is synthesized in epidermal melanocytes, within specialized organelles termed melanosomes, and subsequently transferred to neighboring keratinocytes where it accumulates and shields the nuclear DNA by absorbing and scattering UVR [ 71 , 72 ]. A complex network of keratinocyte and fibroblast-secreted factors such as endothelin-1, alpha stimulating hormone (α- MSH), and stem cell factor (SCF) are described as modulators of the function of melanocytes [ 73 , 74 ].…”

Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages

“…[60][61][62] In addition, opioid β-endorphin can trigger addiction-like responses to UV radiation. [63,64] Activation of μ-and κ-opioid receptors (KOR) is known to mediate opposite effects [65] which makes MOR and KOR attractive targets for research in inflammatory and pruritic skin diseases. [66] MOR antagonists and KOR agonist from various structural classes have been developed up to clinical trials in pruritus of various origins.…”