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

?-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage
?-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 ?-melanocyte-stimulating hormone (?-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of ?-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. ?-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl2, Bclx, Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, ?-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 ?-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by ?-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, ?-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.
0021-9258
5795-5802
Böhm, Markus
cdfe5288-08f1-4466-a2b0-6d6bbbea555f
Wolff, Ilka
64befa92-bb5f-49f9-acc0-a28c427d3a59
Scholzen, Thomas E.
8382a8cb-2e6d-4c74-8e20-257ecad301e0
Robinson, Samantha J.
a0c8dbf3-06f8-4847-a028-840c143ef946
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Luger, Thomas A.
58152471-de0a-4dce-a813-8e02da38b812
Schwarz, Thomas
c51dcbec-88eb-415e-b938-c269d4969b6f
Schwarz, Agatha
7d9b4810-5b45-4ca7-8a12-3162f2c9bf28
Böhm, Markus
cdfe5288-08f1-4466-a2b0-6d6bbbea555f
Wolff, Ilka
64befa92-bb5f-49f9-acc0-a28c427d3a59
Scholzen, Thomas E.
8382a8cb-2e6d-4c74-8e20-257ecad301e0
Robinson, Samantha J.
a0c8dbf3-06f8-4847-a028-840c143ef946
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Luger, Thomas A.
58152471-de0a-4dce-a813-8e02da38b812
Schwarz, Thomas
c51dcbec-88eb-415e-b938-c269d4969b6f
Schwarz, Agatha
7d9b4810-5b45-4ca7-8a12-3162f2c9bf28

Böhm, Markus, Wolff, Ilka, Scholzen, Thomas E., Robinson, Samantha J., Healy, Eugene, Luger, Thomas A., Schwarz, Thomas and Schwarz, Agatha (2005) ?-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).

Record type: Article

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 ?-melanocyte-stimulating hormone (?-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of ?-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. ?-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl2, Bclx, Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, ?-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 ?-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by ?-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, ?-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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Published date: 2005

Identifiers

Local EPrints ID: 26945
URI: https://eprints.soton.ac.uk/id/eprint/26945
ISSN: 0021-9258
PURE UUID: 69ad2a13-b377-4335-b0c5-588658929ecb

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Date deposited: 25 Apr 2006
Last modified: 17 Jul 2017 16:05

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Contributors

Author: Markus Böhm
Author: Ilka Wolff
Author: Thomas E. Scholzen
Author: Samantha J. Robinson
Author: Eugene Healy
Author: Thomas A. Luger
Author: Thomas Schwarz
Author: Agatha Schwarz

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