alpha-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage.
Ultraviolet radiation is a well established epidemiologic risk factor for malignant melanoma. This observation has been linked to the relative resistance of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which consequently leads to accumulation of UVB radiation-induced DNA lesions in melanocytes. Therefore, identification of physiologic factors regulating UVB radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological importance. We show that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of alpha-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. alpha-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl(2), Bcl(x), Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, alpha-MSH markedly reduces the formation of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV radiation-induced DNA damage by alpha-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by alpha-MSH in nucleotide excision repair-deficient fibroblasts. These data, for the first time, demonstrate regulation of UVB radiation-induced apoptosis of human melanocytes by a neuropeptide that is physiologically expressed within the epidermis. Apart from its ability to induce photoprotective melanin synthesis, alpha-MSH appears to exert the capacity to reduce UV radiation-induced DNA damage and, thus, may act as a potent protection factor against the harmful effects of UV radiation on the genomic stability of epidermal cells.
Böhm
Markus
M
Department of Dermatology and the Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Von Esmarch-Str. 58, D-48149 Münster, Germany. bohmm@uni-muenster.de
Wolff
Ilka
I
Scholzen
Thomas E
TE
Robinson
Samantha J
SJ
Healy
Eugene
E
Luger
Thomas A
TA
Schwarz
Thomas
T
Schwarz
Agatha
A
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects*; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008543:Melanins / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000521:alpha-MSH / Q000494:pharmacology*
D008543:Melanins; D011740:Pyrimidine Dimers; D011837:Radiation-Protective Agents; D000521:alpha-MSH