α-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage

Böhm, Markus, Wolff, Ilka, Scholzen, Thomas E., Robinson, Samantha J., Healy, Eugene, Luger, Thomas A., Schwarz, Thomas and Schwarz, Agatha (2005) α-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. The Journal of Biological Chemistry, 280 (7), 5795-5802. (doi:10.1074/jbc.M406334200).

Abstract

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 α-melanocyte-stimulating hormone (α-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of α-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. α-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl₂, Bcl_x, Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, α-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 α-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by α-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, α-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.

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