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首页> 外文期刊>The Journal of investigative dermatology. >Susceptibility of Skin Cells to UVA-induced Necrotic Cell Death Reflects the Intracellular Level of Labile Iron.
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Susceptibility of Skin Cells to UVA-induced Necrotic Cell Death Reflects the Intracellular Level of Labile Iron.

机译：皮肤细胞对UVA诱导的坏死细胞死亡的敏感性反映了不稳定铁的细胞内水平。

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摘要

The mechanism of resistance of keratinocytes to ultraviolet A (UVA) (320-400 nm)-induced oxidative damage has not yet been elucidated. Here, we examined the possible link between the intracellular level of the labile iron pool (LIP) and the susceptibility to UVA-induced cell death using a series of human skin fibroblast and keratinocyte cell lines as a model. Resistance of keratinocytes to UVA-induced cell death was confirmed by flow cytometry and in fibroblasts necrosis was found to be the primary mode of cell death induced by UVA. The percentage of necrosis in fibroblasts also correlated with the extent of intracellular ATP depletion, a hallmark of necrotic cell death. The evaluation of the intracellular level of LIP by calcein assay revealed that both "basal" and UVA-induced in fibroblasts. Accordingly the dose to give an equivalent level of necrosis was several fold lower in fibroblasts than in keratinocytes. Furthermore, the modulation of "basal" or "UVA-induced" level of LIP by either Desferal and/or hemin treatment significantly affected the extent of UVA-induced necrotic cell death and ATP depletion in all the cell lines. Cellular susceptibility to UVA-induced necrotic cell death appears to reflect the intracellular level of LIP.
机译：角质形成细胞对紫外线A（UVA）（320-400 nm）诱导的氧化损伤的抗性机制尚未阐明。在这里，我们使用一系列人类皮肤成纤维细胞和角质形成细胞系作为模型，研究了不稳定铁池（LIP）的细胞内水平与UVA诱导的细胞死亡敏感性之间的可能联系。通过流式细胞术证实了角质形成细胞对UVA诱导的细胞死亡的抗性，并且在成纤维细胞中发现坏死是UVA诱导的细胞死亡的主要模式。成纤维细胞中坏死的百分比也与细胞内ATP消耗的程度相关，后者是坏死细胞死亡的标志。通过钙黄绿素测定法对LIP的细胞内水平的评估表明，“基础”和UVA均在成纤维细胞中诱导。因此，在成纤维细胞中，产生同等坏死水平的剂量要比在角质形成细胞中低几倍。此外，通过Desferal和/或血红素处理对LIP的“基础”或“ UVA诱导”水平的调节显着影响了所有细胞系中UVA诱导的坏死性细胞死亡和ATP耗竭的程度。细胞对UVA诱导的坏死细胞死亡的敏感性似乎反映了LIP的细胞内水平。

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