Role of melanin in melanocyte dysregulation of reactive oxygen species.
Role of melanin in melanocyte dysregulation of reactive oxygen species.
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DOI：
10.1155/2013/908797
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发表时间：
2013
影响因子：
--
通讯作者：
Grossman D
中科院分区：
文献类型：
--
作者：
Jenkins NC;Grossman D
我们最近报道了p16的一种潜在的肿瘤抑制功能，与其调节氧化应激的能力有关，并观察到与角质形成细胞或成纤维细胞相比，p16缺失细胞的氧化失调在黑素细胞中最为严重。此外，在没有p16缺失或外源性氧化损伤的情况下，黑素细胞比其他类型的表皮细胞表现出显著更高的基础活性氧物种(ROS)水平。鉴于氧化应激在黑色素瘤发展中的作用，我们推测，这种增加的黑素细胞对氧化应激的敏感性(以及对p16抑制ROS的更多依赖)可能解释了为什么p16的遗传妥协更常见地与黑色素瘤的易感性有关，而不是其他癌症。在这里，我们表明，黑色素的存在解释了正常和p16耗尽的黑素细胞中这种不同的氧化应激。因此，皮肤中黑色素的存在似乎是一把双刃剑：它通过吸收紫外线辐射来保护皮肤中的黑素细胞和邻近的角质形成细胞，但它在黑素细胞中的合成导致细胞内ROS水平升高，这可能会增加黑色素瘤的易感性。
We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS) may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.