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Clock genes modulation by UVA/blue light stimulation in normal melan-A and transformed B-16 melanocytes

Grant number: 13/24337-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2014
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Ana Maria de Lauro Castrucci
Grantee:Leonardo Vinícius Monteiro de Assis
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/50214-4 - Biological clock setting by light and temperature: phylogenetic aspects, AP.TEM


Environmental light-dark cycles evoke several physiological and behavioral responses in animals. In mammals, the suprachiasmatic nucleus (SCN) is the pacemaker responsible for generating the self-sustainable rhythms with a period close to 24 hours called circadian rhythms. Input signals such as light and temperature can reset the suprachiasmatic clock in a daily basis synchronizing the circadian rhythm to precisely 24 hours of the day. Besides the central clock there are also peripheral clocks spread throughout cells and tissues within the organism, which are under hierarchical influence of the central clock. Per, Cry, Clock and Bmal1 genes share an important role in generating these rhythms, through complex inhibition and activation mechanisms. Studies have shown an important correlation between circadian disruption and cancer development in shift workers. Although little is known about the mechanisms involved in this process, it is known that genes related to apoptosis, cell cycle and DNA repair display circadian oscillations and might be under circadian control. The super family of Transient Receptor Potential channel (TRP) is important in regulating several cellular processes, such as: temperature and pain detection, UV light response and early melanin synthesis. Interestingly, it has been demonstrated that UV light is able to interact with members of this family, through activation of rhodopsin, leading to rapid and sustained influx of calcium, which ultimately generates an early pigmentation in human melanocytes. Part of this phenomenon might be due to free radical generation; however, it is not known whether UVA/blue light interacts with TRP channels and free radicals to modulate clock gene expression. That would possibly characterize a route for peripheral clock adjustment and cell cycle control, which would ultimately promote or not cancer development. Therefore, the aim of this project is to study the modulation of clock genes through the UV/blue light stimulation in normal and transformed melanocytes. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Investigation of body clock could point to target for treatment of skin cancer 

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MONTEIRO DE ASSIS, LEONARDO VINICIUS; MENDES, DAVI; SILVA, MATHEUS MOLINA; KINKER, GABRIELA SARTI; PEREIRA-LIMA, ISABELLA; MORAES, MARIA NATHALIA; MARTINS MENCK, CARLOS FREDERICO; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin mediates UVA-dependent modulation of proliferation, pigmentation, apoptosis, and molecular clock in normal and malignant melanocytes. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1867, n. 10 OCT 2020. Web of Science Citations: 0.
HERMIDORFF, MILLA MARQUES; MONTEIRO DE ASSIS, LEONARDO VINICIUS; RODRIGUES, JOEL ALVES; SOARES, LEONCIO LOPES; GUERRA ANDRADE, MILTON HERCULES; NATALI, ANTONIO JOSE; ISOLDI, MAURO CESAR. Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters. HEART AND VESSELS, v. 35, n. 5, p. 719-730, MAY 2020. Web of Science Citations: 0.
MONTEIRO DE ASSIS, LEONARDO VINICIUS; KINKER, GABRIELA SARTI; MORAES, MARIA NATHALIA; MARKUS, REGINA P.; FERNANDES, PEDRO AUGUSTO; DE LAURO CASTRUCCI, ANA MARIA. Expression of the Circadian Clock Gene BMAL1 Positively Correlates With Antitumor Immunity and Patient Survival in Metastatic Melanoma. FRONTIERS IN ONCOLOGY, v. 8, JUN 12 2018. Web of Science Citations: 6.
MONTEIRO DE ASSIS, LEONARDO VINICIUS; MORAES, MARIA NATHALIA; MAGALHAES-MARQUES, KEILA KAROLINE; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin and rhodopsin mediate UVA-induced immediate pigment darkening: Unravelling the photosensitive system of the skin. EUROPEAN JOURNAL OF CELL BIOLOGY, v. 97, n. 3, p. 150-162, APR 2018. Web of Science Citations: 8.
DE ASSIS, L. V. M.; MORAES, M. N.; DA SILVEIRA CRUZ-MACHADO, S.; CASTRUCCI, A. M. L. The effect of white light on normal and malignant murine melanocytes: A link between opsins, clock genes, and melanogenesis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1863, n. 6, A, p. 1119-1133, JUN 2016. Web of Science Citations: 19.
LOCATELLI, JAMILLE; MONTEIRO DE ASSIS, LEONARDO VINICIUS; ARAUJO, CAROLINA MORAIS; ALZAMORA, ANDREIA CARVALHO; DE LIMA, WANDERSON GERALDO; CAMPAGNOLE-SANTOS, MARIA JOSE; DOS SANTOS, ROBSON AUGUSTO; ISOLDI, MAURO CESAR. Swimming training promotes cardiac remodeling and alters the expression of mRNA and protein levels involved in calcium handling in hypertensive rats. Life Sciences, v. 117, n. 2, p. 67-74, NOV 11 2014. Web of Science Citations: 8.
LEONARDO VINÍCIUS MONTEIRO DE ASSIS; MAURO CÉSAR ISOLDI. Overview of the biochemical and genetic processes in malignant mesothelioma. Jornal Brasileiro de Pneumologia, v. 40, n. 4, p. -, Ago. 2014.

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