Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes.
UV-induced melanogenesis is a well known physiological response of human skin exposed to solar radiation; however, the signaling molecules involved in the stimulation of melanogenesis in melanocytes following UV exposure remain unclear. In this study we induced melanogenesis in vitro in normal human epidermal melanocytes using a single irradiation with UVA at 1 kJ/m2 and examined the potential involvement of mitogen-activated protein kinases (MAPK) as UVA-responsive signaling molecules in those cells. UVA irradiation did not affect the proliferation of melanocytes, but it did increase tyrosinase mRNA expression, which reached a maximum level 4 hr after UVA irradiation. The amount of tyrosinase protein, as quantitated by immunoblotting, was also increased at 24 hr following UVA irradiation. Among the MAPK examined, extracellular signal-related kinase (ERK) 1/2 was phosphorylated within 15 min of UVA irradiation, but no such phosphorylation was observed for c-Jun N-terminal kinases (JNK) or p38. Accordingly, the activity of ERK1/2 was also increased shortly after UVA irradiation. These responses of ERK1/2 to UVA irradiation were markedly inhibited when cells were pre-treated with N-acetyl-L-cysteine, an antioxidant, or with suramin, a tyrosine kinase receptor inhibitor. The formation of (6-4)photoproducts or cyclobutane pyrimidine dimers was not detected in cellular DNA after UVA irradiation. These findings suggest that a single UVA irradiation-induced melanogenesis is associated with the activation of ERK1/2 by upstream signals that originate from reactive oxygen species or from activated tyrosine kinase receptors, but not from damaged DNA.
Yanase
H
H
Technical Research Laboratory, Kurabo Industries Ltd, Osaka, Japan.
Ando
H
H
Horikawa
M
M
Watanabe
M
M
Mori
T
T
Matsuda
N
N
D000111:Acetylcysteine / Q000494:pharmacology; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008543:Melanins / Q000378:metabolism / Q000528:radiation effects; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
D016166:Free Radical Scavengers; D008543:Melanins; D017382:Reactive Oxygen Species; D014442:Monophenol Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000111:Acetylcysteine