Significance of melanin distribution in the epidermis for the protective effect against UV light

Abstract

Melanin, the most abundant skin chromophore, is produced by melanocytes and is one of the key components responsible for mediating the skin’s response to ultraviolet radiation (UVR). Because of its antioxidant, radical scavenging, and broadband UV absorbing properties, melanin reduces the penetration of UVR into the nuclei of keratinocytes. Despite its long-established photoprotective role, there is evidence that melanin may also induce oxidative DNA damage in keratinocytes after UV exposure and therefore be involved in the development of melanoma. The present work aimed at evaluating the dependence of UV-induced DNA damage on melanin content and distribution, using reconstructed human epidermis (RHE) models. Tanned and light RHE were irradiated with a 233 nm UV-C LED source at 60 mJ/cm2 and a UV lamp at 3 mJ/cm2. Higher UV-mediated free radicals and DNA damage were detected in tanned RHE with significantly higher melanin content than in light RHE. The melanin distribution in the individual models can explain the lack of photoprotection. Fluorescence lifetime-based analysis and Fontana–Masson staining revealed a non-homogeneous distribution and absence of perinuclear melanin in the tanned RHE compared to the in vivo situation in humans. Extracellularly dispersed epidermal melanin interferes with photoprotection of the keratinocytes.

Melanin for Photoprotection and Hair Coloration in the Emerging Era of Nanocosmetics

“…Moreover, the photoprotective action of melanin on the skin is still not clearly understood. Indeed, as reported in the recent study of Zamudio Díaz et al [ 64 ], melanin could also induce DNA damage. Indeed, in some cases, it seems to act as a photosensitizer rather than as a photoprotective agent: UV-induced radical species can indeed degrade melanin, leading to species which could transfer their energy to DNA bases.…”

“…The exposure of our skin to UV radiation has numerous effects in our bodies, such as the synthesis of vitamin D and endorphins, tanning, and immunoregulation [ 63 ]. However, overexposure to UV radiation has been reported to induce DNA damage and skin cancer [ 64 , 65 ]. The strategy that the human organism adopts to contrast the negative effects of UV radiation is the production of melanin as a photoprotective agent.…”

Petanin Potentiated JNK Phosphorylation to Negatively Regulate the ERK/CREB/MITF Signaling Pathway for Anti-Melanogenesis in Zebrafish

“…Despite its long-established photoprotective role, there is evidence that melanin may also induce oxidative DNA damage in keratinocytes after UV exposure, and α-melanocyte-stimulating hormone (α-MSH) secreted from keratinocytes activates the melanocortin receptor 1 (MC1R) on the surface of melanocytes, which in turn triggers cAMP generation and PKA activation. It then translocates to the cell nucleus and phosphorylates CREB at Ser133, facilitating its binding with the CREB-binding protein, which enhances the expression of MITF and induction of downstream melanogenic genes [ 13 , 14 , 15 ]. MITF regulates the development of several cell types, including melanocytes, and is a key regulating transcription factor in melanocytes, responding to UVR [ 16 , 17 , 18 ].…”

Multiphoton skin biopsy

“…MPT as a clinical imaging method was introduced in 2003 by two-photon imaging of patients with suspicious pigmented lesions at the University of Jena. In 2004, the commercial multiphoton tomograph DermaInspect became the first certified medical device dedicated to medical femtosecond laser imaging [8][9][10] MPT provides optical skin biopsies based on femtosecond laser-induced autofluorescence (AF) and second harmonic generation (SHG) of collagen. Recently, a multimodal multiphoton tomograph 11 was introduced that employs nearinfrared 50/80 MHz laser pulses for both multiphoton imaging and RCM.…”