Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: regulation by ultraviolet B.
It is demonstrated that ultraviolet B (UVB) radiation stimulates increased expression of the proopiomelanocortin (POMC) gene which is accompanied by production and release of alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) by both normal and malignant human melanocytes and keratinocytes. The production and release of both peptides are also stimulated by dibutyryl cyclic adenosine monophosphate (dbcAMP) and interleukin 1 alpha (IL-1 alpha) but not by endothelin-1 (ET-1) or tumor necrosis factor-alpha (TNF-alpha). N-acetyl-cysteine (NAC), a precursor of glutathione (GSH), an intracellular free radical scavenger, abolishes the UVB-stimulated POMC peptide production and secretion. Conclusions are as follows: (1) Cultured human cells of cutaneous origin, namely keratinocytes and melanocytes, can produce and express POMC; (2) POMC expression is enhanced by exposure to UVB, possibly through a cyclic AMP-dependent pathway; and (3) The action of UVB on POMC production may involve a cellular response to oxidative stress.
Chakraborty
A K
AK
Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
Funasaka
Y
Y
Slominski
A
A
Ermak
G
G
Hwang
J
J
Pawelek
J M
JM
Ichihashi
M
M
D000111:Acetylcysteine / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D016232:Endothelins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D008544:Melanocytes / Q000502:physiology*; D008969:Molecular Sequence Data; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D016207:Cytokines; D017931:DNA Primers; D016232:Endothelins; D012333:RNA, Messenger; D003994:Bucladesine; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine