TY - JOUR
T1 - Melanopsin, a Canonical Light Receptor, Mediates Thermal Activation of Clock Genes
AU - Moraes, Maria Nathália
AU - De Assis, Leonardo Vinícius Monteiro
AU - Magalhães-Marques, Keila Karoline
AU - Poletini, Maristela Oliveira
AU - De Lima, Leonardo Henrique Ribeiro Graciani
AU - De Lauro Castrucci, Ana Maria
N1 - Funding Information:
This work was partially supported by the Sao Paulo Research Foundation (FAPESP, grant 2012/50214-4) and by the National Council of Technological and Scientific Development (CNPq, grants 301293/2011-2 and 303070/2015-3). MN Moraes, LVM de Assis, and LHRG Lima are fellows of FAPESP (2014/16412-9, 2013/24337-4 and 2009/53533-0 respectively). We are thankful to Prof. Ignacio Provencio from the University of Virginia for providing theoretical and methodological insights and thoughtful discussions.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects of heat shock on the localization of melanopsin by immunocytochemistry. In both cell lines melanopsin was found in a region capping the nucleus and heat shock did not affect its location. The heat-induced increase of Per1 expression was inhibited when melanopsin was pharmacologically blocked by AA92593 as well as when its protein expression was suppressed by siRNA in both Melan-a and B16-F10 cells. These data strongly suggest that melanopsin is required for thermo-reception, acting as a thermo-opsin that ultimately feeds the local circadian clock in mouse melanocytes and melanoma cells.
AB - Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects of heat shock on the localization of melanopsin by immunocytochemistry. In both cell lines melanopsin was found in a region capping the nucleus and heat shock did not affect its location. The heat-induced increase of Per1 expression was inhibited when melanopsin was pharmacologically blocked by AA92593 as well as when its protein expression was suppressed by siRNA in both Melan-a and B16-F10 cells. These data strongly suggest that melanopsin is required for thermo-reception, acting as a thermo-opsin that ultimately feeds the local circadian clock in mouse melanocytes and melanoma cells.
UR - http://www.scopus.com/inward/record.url?scp=85032175524&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-13939-3
DO - 10.1038/s41598-017-13939-3
M3 - Journal articles
C2 - 29070825
AN - SCOPUS:85032175524
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13977
ER -
