Melanocyte-stimulating hormone directly enhances UV-Induced DNA repair in keratinocytes by a xeroderma pigmentosum group A-dependent mechanism.
Melanocyte-stimulating hormone directly enhances UV-Induced DNA repair in keratinocytes by a xeroderma pigmentosum group A-dependent mechanism.
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DOI：
10.1158/0008-5472.can-09-4596
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发表时间：
2010-05-01
期刊：
影响因子：
11.2
通讯作者：
Cui R
中科院分区：
文献类型：
--
作者：
Dong L;Wen J;Pier E;Zhang X;Zhang B;Dong F;Ziegler N;Mysz M;Armenta R;Cui R
促黑素细胞激素（MSH）通过诱导色素沉着减少UV诱导的DNA损伤。在这项研究中，我们提供的证据表明，MSH也通过调节DNA修复分子的功能，增强皮肤角质形成细胞的DNA修复。皮内注射的MSH防止紫外线诱导的DNA损伤在人类和小鼠皮肤独立的黑素生成的影响。在角质形成细胞中，MSH与黑素细胞黑皮质素受体1型（MC1R）结合并激活腺苷酸环化酶活性，进而激活XPA结合蛋白1（XAB 1）并诱导XPA核转位，XPA是控制核苷酸切除修复（NER）信号通路的关键因子。总之，我们的研究结果揭示了一种新的色素不依赖性机制，其基础是UVB照射后MSH介导的DNA修复。
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 (MC1R) and activated adenylate cyclase activity, which in turn activated XPA binding protein 1 (XAB1) and induced nuclear translocation of XPA, a critical factor controlling nucleotide excision repair (NER) signaling pathways. Together, our findings reveal a novel pigmentation-independent mechanism that underlies MSH-mediated DNA repair following UVB irradiation.