Melanopsin mediates UVA-dependent modulation of proliferation, pigmentation, apoptosis, and molecular clock in normal and malignant melanocytes

Author(s)

Monteiro de Assis, Leonardo Vinicius ^[1] ; Mendes, Davi ^[2] ; Silva, Matheus Molina ^[2] ; Kinker, Gabriela Sarti ^[3] ; Pereira-Lima, Isabella ^[1] ; Moraes, Maria Nathalia ^[4] ; Martins Menck, Carlos Frederico ^[2] ; de Lauro Castrucci, Ana Maria ^{[5, 1]}

Affiliation

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

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, DNA Repair Lab, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Neuroimmunoendocrinol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Lab Neurobiol, Sao Paulo - Brazil

^[5] Univ Virginia, Dept Biol, Charlottesville, VA - USA

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1867, n. 10 OCT 2020.
• Web of Science Citations: 0

Abstract

Cutaneous melanocytes and melanoma cells express several opsins, of which melanopsin (OPN4) detects temperature and UVA radiation. To evaluate the interaction between OPN4 and UVA radiation, normal and malignant Opn4(WT) and Opn4(KO) melanocytes were exposed to three daily low doses (total 13.2 kJ/m(2)) of UVA radiation. UVA radiation led to a reduction of proliferation in both Opn4(WT) cell lines; however, only in melanoma cells this effect was associated with increased cell death by apoptosis. Daily UVA stimuli induced persistent pigment darkening (PPD) in both Opn4(WT) cell lines. Upon Opn4 knockout, all UVA-induced effects were lost in three independent clones of Opn4(KO) melanocytes and melanoma cells. Perl bioluminescence was reduced after 1st and 2nd UVA radiations in Opn4(WT) cells. In Opn4(KO) melanocytes and melanoma cells, an acute increase of Per1 expression was seen immediately after each stimulus. We also found that OPN4 expression is downregulated in human melanoma compared to normal skin, and it decreases with disease progression. Interestingly, metastatic melanomas with low expression of OPN4 present increased expression of BMAL1 and longer overall survival. Collectively, our findings reinforce the functionality of the photosensitive system of melanocytes that may subsidize advancements in the understanding of skin related diseases, including cancer. (AU)

• FAPESP's process: 14/27287-0 - Characterization of the melatonergic system of human gliomas and its implication on tumor aggressiveness and invasiveness
• Grantee: Gabriela Sarti Kinker
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/24337-4 - Clock genes modulation by UVA/blue light stimulation in normal melan-A and transformed B-16 melanocytes
• Grantee: Leonardo Vinícius Monteiro de Assis
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/24615-5 - Breaking a paradigm? Melanopsin, a canonical photo-pigment, acting as sensor to entrain the clock in light unexposed organs, and its putative interaction with TRP channels: a trans-disciplinary study involving physiological and pathological aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/50214-4 - Biological clock setting by light and temperature: phylogenetic aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/16511-8 - Involvement of the photosensitive and temporal controlling systems in the development, progression, and metastasis of malignant melanoma: an investigation of novel therapeutic targets
• Grantee: Leonardo Vinícius Monteiro de Assis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism
• Grantee: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/18781-0 - The role of XPG endonuclease in nuclear RNA transcription and in the maintenance of mitochondrial genome
• Grantee: Davi Mendes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/14728-0 - Melanopsin as the UVA photoreceptor and its relationship with pigmentation, DNA repair, biological clock and components of the HPA axis: a novel pharmacological target?
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/24217-0 - Mechanisms of tumor resistance to cisplatin: DNA lesions processing and circadian cycle effect
• Grantee: Matheus Molina Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)