Melanopsin and rhodopsin mediate UVA-induced immediate pigment darkening: Unravelling the photosensitive system of the skin

Autor(es)

Monteiro de Assis, Leonardo Vinicius ^[1] ; Moraes, Maria Nathalia ^[1] ; Magalhaes-Marques, Keila Karoline ^[1] ; de Lauro Castrucci, Ana Maria ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Comparat Physiol Pigmentat, Sao Paulo - Brazil

^[2] Univ Virginia, Dept Biol, Charlottesville, VA - USA

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF CELL BIOLOGY; v. 97, n. 3, p. 150-162, APR 2018.
• Citações Web of Science: 8

Resumo

The mammalian skin has a photosensitive system comprised by several opsins, including rhodopsin (OPN2) and melanopsin (OPN4). Recently, our group showed that UVA (4.4 kJ/m(2)) leads to immediate pigment darkening (IPD) in murine normal and malignant melanocytes. We show the role of OPN2 and OPN4 as UVA sensors: UVA-induced IPD was fully abolished when OPN4 was pharmacologically inhibited by AA9253 or when OPN2 and OPN4 were knocked down by siRNA in both cell lines. Our data, however, demonstrate that phospholipase C/protein kinase C pathway, a classical OPN4 pathway, is not involved in WA-induced IPD in either cell line. Nonetheless, in both cell types we have shown that: a) intracellular calcium signal is necessary for WA-induced IPD; b) the involvement of CaMK II, whose inhibition, abolished the UVA-induced IPD; c) the role of CAMK II/NOS/sGC/cGMP pathway in the process since inhibition of either NOS or sGC abolished the WA-induced IPD. Taken altogether, we show that OPN2 and OPN4 participate in IPD induced by WA in murine normal and malignant melanocytes through a conserved common pathway. Interestingly, upon knockdown of OPN2 or OPN4, the UVA-driven IPD is completely lost, which suggests that both opsins are required and cooperatively signal in murine both cell lines. The participation of OPN2 and OPN4 system in UVA radiation-induced response, if proven to take place in human skin, may represent an interesting pharmacological target for the treatment of depigmentary disorders and skin-related cancer. (AU)

• Processo FAPESP: 14/16412-9 - Mecanismos de termo-modulação de genes de relógio em tecidos periféricos de mamíferos: papel dos canais TRP
• Beneficiário: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/24337-4 - Mecanismos de modulação de genes de relógio em melanócitos normais (melan-A) e transformados (melanoma B16-F10) por UVA e luz azul
• Beneficiário: Leonardo Vinícius Monteiro de Assis
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 12/50214-4 - Mecanismos de ajuste do relógio por luz e temperatura: aspectos filogenéticos
• Beneficiário: Ana Maria de Lauro Castrucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático