Apoptosis may underlie the pathology of zinc-deficient skin
Apoptosis may underlie the pathology of zinc-deficient skin
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DOI：
10.1111/j.1440-1711.2005.01391.x
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Ackland, ML
中科院分区：
文献类型：
--
作者：
Wilson, D;Varigos, G;Ackland, ML
微量元素锌对所有细胞的生存和功能都是必不可少的。锌缺乏，无论是营养性的还是遗传性的，如果不治疗，都是致命的。缺锌的影响在皮肤上特别明显，表现为红斑疹、鳞片斑块和溃疡。电子显微镜显示角质形成细胞内有退行性改变。尽管锌缺乏与皮肤病理之间的关系已经得到了很好的证明，但尚不清楚哪些细胞过程对锌缺乏最敏感，并可能解释典型的病理特征。我们使用培养的HaCaT角质形成细胞系来深入了解缺锌对细胞的影响，因为这些细胞表现出正常皮肤角质形成细胞的许多特征。缺锌是通过在锌螯合剂TPEN存在的情况下生长细胞或在缺锌介质中生长来诱导的。细胞在缺锌条件下生长，细胞内锌含量下降44%，锌依赖酶5‘-核苷酸酶活性下降75%。在暴露于缺锌条件下的7天期间，HaCaT细胞的细胞活力和生长没有变化，细胞骨架和细胞黏附系统也没有变化。然而，在第7天，细胞内出现DNA片段化和活性caspase-3的表达，表明诱导了细胞的凋亡。这些结果表明，细胞凋亡是缺锌诱导的HaCaT角质形成细胞最早可检测到的变化。我们的观察解释了缺锌的许多特征，包括变性核的存在，染色质聚集和角蛋白的异常组织，这可能代表了细胞凋亡的后期。综上所述，细胞凋亡在皮肤缺锌的病理中起着重要的作用。这一作用与之前在缺锌角质形成细胞超微结构水平上看到的未知的不同范围的退行性细胞变化是一致的。
The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenerative changes within keratinocytes. Despite the well-documented association between zinc deficiency and skin pathology, it is not clear which cellular processes are most sensitive to zinc deficiency and could account for the typical pathological features. We used the cultured HaCaT keratinocyte line to obtain insight into the cellular effects of zinc deficiency, as these cells show many characteristics of normal skin keratinocytes. Zinc deficiency was induced by growing cells in the presence of the zinc chelator, TPEN, or by growth in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a 44% reduction of intracellular zinc levels and a 75% reduction in the activity of the zinc-dependent enzyme, 5'-nucleotidase, relative to the control cells. Over a period of 7 days of exposure to zinc-deficient conditions, no changes in cell viability and growth, or in the cytoskeletal and cell adhesion systems, were found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by the presence of DNA fragmentation and expression of active caspase-3 in cells. These results demonstrate that apoptosis is the earliest detectable cellular change induced by zinc deficiency in HaCaT keratinocytes. Our observations account for many of the features of zinc deficiency, including the presence of degenerate nuclei, chromatin aggregates and abnormal organization of keratin, that may represent the later stages of apoptosis. In summary, a major causal role for apoptosis in the pathology of zinc deficiency in the skin is proposed. This role is consistent with the previously unexplained diverse range of degenerative cellular changes seen at the ultrastructural level in zinc-deficient keratinocytes.