title: The effect of white light on normal and malignant murine melanocytes: A link between opsins, clock genes, and melanogenesis.
abstract: The skin possesses a photosensitive system comprised of opsins whose function is not fully understood, and clock genes which exert an important regulatory role in skin biology. Here, we evaluated the presence of opsins in normal (Melan-a cells) and malignant (B16-F10 cells) murine melanocytes. Both cell lines express Opn2, Opn4--for the first time reported in these cell types--as well as S-opsin. OPN4 protein was found in a small area capping the cell nuclei of B16-F10 cells kept in constant dark (DD); twenty-four hours after the white light pulse (WLP), OPN4 was found in the cell membrane. Despite the fact that B16-F10 cells expressed less Opn2 and Opn4 than Melan-a cells, our data indicate that the malignant melanocytes exhibited increased photoresponsiveness. The clock gene machinery is also severely downregulated in B16-F10 cells as compared to Melan-a cells. Per1, Per2, and Bmal1 expression increased in B16-F10 cells in response to WLP. Although no response in clock gene expression to WLP was observed in Melan-a cells, gene correlational data suggest a minor effect of WLP. In contrast to opsins and clock genes, melanogenesis is significantly upregulated in malignant melanocytes in comparison to Melan-a cells. Tyrosinase expression increased after WLP only in B16-F10 cells; however no increase in melanin content after WLP was seen in either cell line. Our findings may prove useful in the treatment and the development of new pharmacological approaches of depigmentation diseases and skin cancer.
authors.affiliation: Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: L V M
authors.initials: LV
authors.lastname: de Assis
authors.affiliation: Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: M N
authors.initials: MN
authors.lastname: Moraes
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: da Silveira Cruz-Machado
authors.affiliation: Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil. Electronic address: amdlcast@ib.usp.br.
authors.forename: A M L
authors.initials: AM
authors.lastname: Castrucci
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000528:radiation effects*; D007150:Immunohistochemistry; D008027:Light; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D055355:Opsins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D008543:Melanins; D055355:Opsins; D012333:RNA, Messenger; D014442:Monophenol Monooxygenase; D056926:CLOCK Proteins
keywords: Cancer; Clock genes; Melanocytes; Melanoma; Mouse; Opsins