title: UVA phototransduction drives early melanin synthesis in human melanocytes.
abstract: Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin.
authors: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA.
authors: Nadine L
authors: NL
authors: Wicks
authors: Jason W
authors: JW
authors: Chan
authors: Julia A
authors: JA
authors: Najera
authors: Jonathan M
authors: JM
authors: Ciriello
authors: Elena
authors: E
authors: Oancea
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects*; D005470:Fluorometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D055537:Light Signal Transduction; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects*; D016133:Polymerase Chain Reaction; D012172:Retinaldehyde / Q000737:chemistry / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D008543:Melanins; D012243:Rhodopsin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D012172:Retinaldehyde; D002118:Calcium