Molecular responses to stress induced in normal human Caucasian melanocytes in culture by exposure to simulated solar UV
Molecular responses to stress induced in normal human Caucasian melanocytes in culture by exposure to simulated solar UV
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DOI：
10.1562/2004-10-13-ra-343.1
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Meunier, JR
中科院分区：
文献类型：
--
作者：
Marrot, L;Belaïdi, JP;Meunier, JR
黑素细胞在皮肤对阳光照射的反应中起着核心作用。它们直接参与紫外线诱导的色素沉着，作为一种防御机制。然而，它们的改变可能会导致黑色素瘤，这一过程中阳光过度曝光的作用非常可能。紫外线损伤可能导致黑色素瘤的转化过程尚不清楚，特别是在紫外线诱导的色素细胞中的遗传毒性方面，其中黑色素既可以作为防晒剂，也可以作为光敏剂。这项研究的目的是分析白皙皮肤黑素细胞在模拟环境阳光照射下的光谱能量分布行为。为此，培养的正常人黑素细胞暴露在模拟太阳紫外线(SSUV，300-400 nm)中。即使在相对较高的剂量下(直到20分钟，相当于12kJ/m(2)UV-B和110kJ/m(2)UV-A)，细胞死亡也是有限的，这表现为细胞存活和较低的凋亡发生率(caspase-3激活)。此外，在SSUV照射后，黑素细胞中P53的积累量比成纤维细胞等无色素细胞中的P53积累量低三倍。然而，一个重要的黑素细胞群体被滞留在G2-M期，这与暴露后4小时GADD45基因的高诱导水平有很好的相关性。在参与DNA修复的基因中，XPC基因是最容易诱导的基因，其表达在暴露20min后15h增加一倍以上，而P48的表达仅略有增加。此外，还首次在黑素细胞中观察到了血红素加氧酶1(HO1)基因的早期诱导，这是一种典型的对氧化应激的反应。有趣的是，当黑素细胞只暴露在UV-A辐射(320400 Nm)下时，这种诱导仍然显著，并且在照射前刺激黑素合成进一步增加了HO1的诱导。这些结果是在正常人体细胞暴露于SSUV辐射后获得的，SSUV辐射模拟自然阳光。他们提供了与基因表达相关的新数据，并表明浅色皮肤中的黑色素可能有助于阳光诱导的遗传毒性，可能还有助于黑素细胞的转化。
Melanocytes play a central role in the response of skin to sunlight exposure. They are directly involved in UV-induced pigmentation as a defense mechanism. However, their alteration can lead to melanoma, a process where the role of sun overexposure is highly probable. The transformation process whereby UV damage may result in melanoma initiation is poorly understood, especially in terms of UV-induced genotoxicity in pigmented cells, where melanin can act either as a sunscreen or as a photosensitizer. The aim of this study was to analyze the behavior of melanocytes from fair skin under irradiation mimicking environmental sunlight in terms of spectral power distribution. To do this, normal human Caucasian melanocytes in culture were exposed to simulated solar UV (SSUV, 300-400 nm). Even at relatively high doses (until 20 min exposure, corresponding to 12 kJ/m(2) UV-B and 110 kJ/m(2) UV-A), cell death was limited, as shown by cell viability and low occurrence of apoptosis (caspase-3 activation). Moreover, p53 accumulation was three times lower in melanocytes than in unpigmented cells such as fibroblasts after SSUV exposure. However, an important fraction of melanocyte population was arrested in G2-M phase, and this correlated well with a high induction level of the gene GADD45, 4 h after exposure. Among the genes involved in DNA repair, gene XPC was the most inducible because its expression increased more than two-fold 15 h after a 20 min exposure, whereas expression of P48 was only slightly increased. In addition, an early induction of Heme Oxygenase 1 (HO1) gene, a typical response to oxidative stress, was also observed for the first time in melanocytes. Interestingly, this induction remained significant when melanocytes were exposed to UV-A radiation only (320400 nm), and stimulation of melanogenesis before irradiation further increased HO1 induction. These results were obtained with normal human cells after exposure to SSUV radiation, which mimicked natural sunlight. They provide new data related to gene expression and suggest that melanin in light skin could contribute to sunlight-induced genotoxicity and maybe to melanocyte transformation.