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MC1R expression in HaCaT keratinocytes inhibits UVA‐induced ROS production via NADPH Oxidase‐ and cAMP‐dependent mechanisms
Author(s) -
Henri Pauline,
Beaumel Sylvain,
Guezennec Anne,
Poumès Carine,
Stoebner PierreEmmanuel,
Stasia MarieJosé,
Guesnet Joëlle,
Martinez Jean,
Meunier Laurent
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22996
Subject(s) - hacat , melanocortin 1 receptor , melanocyte , keratinocyte , kinase , reactive oxygen species , protein kinase a , microbiology and biotechnology , nadph oxidase , cell culture , biology , chemistry , biochemistry , cancer research , melanoma , phenotype , gene , genetics
Ultraviolet A (UVA) radiations are responsible for deleterious effects, mainly due to reactive oxygen species (ROS) production. Alpha‐melanocyte stimulating hormone (α‐MSH) binds to melanocortin‐1 receptor (MC1R) in melanocytes to stimulate pigmentation and modulate cutaneous inflammatory responses. MC1R may be induced in keratinocytes after UV exposure. To investigate the effect of MC1R signaling on UVA‐induced ROS (UVA‐ROS) production, we generated HaCaT cells that stably express human MC1R (HaCaT‐MC1R) or the Arg151Cys (R 151 C) non‐functional variant (HaCaT‐R 151 C). We then assessed ROS production immediately after UVA exposure and found that: (1) UVA‐ROS production was strongly reduced in HaCaT‐MC1R but not in HaCaT‐R 151 C cells compared to parental HaCaT cells; (2) this inhibitory effect was further amplified by incubation of HaCaT‐MC1R cells with α‐MSH before UVA exposure; (3) protein kinase A (PKA)‐dependent NoxA1 phosphorylation was increased in HaCaT‐MC1R compared to HaCaT and HaCaT‐R 151 C cells. Inhibition of PKA in HaCaT‐MC1R cells resulted in a marked increase of ROS production after UVA irradiation; (4) the ability of HaCaT‐MC1R cells to produce UVA‐ROS was restored by inhibiting epidermal growth factor receptor (EGFR) or extracellular signal‐regulated kinases (ERK) activity before UVA exposure. Our findings suggest that constitutive activity of MC1R in keratinocytes may reduce UVA‐induced oxidative stress via EGFR and cAMP‐dependent mechanisms. J. Cell. Physiol. 227: 2578–2585, 2012. © 2011 Wiley Periodicals, Inc.