Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Abstract

Melanocyte-stimulating hormone (MSH) reduces UV-induced DNA damage through the induction of pigmentation. In this study, we provide evidence that MSH also enhances DNA repair in skin keratinocytes by modulating the function of DNA repair molecules. Intracutaneous injection of MSH prevented UV-induced DNA damage in human and mouse skin independent of its effects on melanogenesis. In keratinocytes, MSH bound to the melanocyte melanocortin receptor type 1 and activated adenylate cyclase activity, which in turn activated Xeroderma pigmentosum group A (XPA)-binding protein 1 and induced nuclear translocation of XPA, a critical factor controlling nucleotide excision repair signaling pathways. Together, our findings reveal a novel pigmentation-independent mechanism that underlies MSH-mediated DNA repair following UVB irradiation. Cancer Res; 70(9); 3547-56. ©2010 AACR.

Proanthocyanidins Inhibit Photocarcinogenesis through Enhancement of DNA Repair and Xeroderma Pigmentosum Group A–Dependent Mechanism

“…Here we also demonstrated that dietary GSPs induces or augments XPA nuclear translocation and then activates the core incision complex in the NER system. Similar observations related with the role of XPA in DNA repair in UVB-exposed skin cells were also found by the treatment of a-melanocytestimulating hormone (35). Stoner et al have studied the effect of diet containing freeze-dried black raspberries on chemical carcinogen N-nitrosomethylbenzylamineinduced dysregulated genes in rat esophagus (36).…”

Paulownia tomentosa (Princess Tree) Extract Reduces DNA Damage and Induces DNA Repair Processes in Skin Cells

“…These diseases are characterized at the level of the skin by extreme sensitivity to sunlight, resulting in sunburn, pigmentation changes, an early onset of the appearance of skin aging signs and a greatly elevated incidence of skin cancers in particular for XP disorder [12]. These changes can be explained by long lasting DNA damages that induces prolonged cellular inflammation through the activation of the NF-κB pathway [2,13,14,15,16] and an acquired immune deficiency [17] as well as rapid accumulation of mutation leading to cell apoptosis, senescence and cell tumorigenesis [18,19,20,21].…”

“…The activation of the Melanocortin Receptor 1 (MCR1) by either its natural ligand, the α-Melanocyte stimulating Hormone αMSH or synthetic analogs [20,21] can enhance the DNA repair activity in cells. Also two interleukins (IL), IL12 and IL23 known to display anti-tumor activity [45,46,47,48] have been shown to accelerate the repair of UVB induced CPDs [2].…”

Regulation of DNA Repair Process by the Pro-Inflammatory NF-κB Pathway

“…The activation of the Melanocortin Receptor 1 (MCR1) by either its natural ligand, the α-Melanocyte stimulating Hormone αMSH or synthetic analogs [17,18] can enhance the DNA repair activity in cells. Also two interleukins (IL), IL12 and IL23, known to display anti-tumor activity [19][20][21][22], have been shown to accelerate the repair of UVB induced CPDs. Activation of detoxifying mechanisms such as the NRf2 pathway may enhance also DNA repair [23].…”