Institute for Bioanalysis, Coburg University of Applied Sciences and Arts Coburg, Friedrich-Streib-Straße 2, D-96450 Coburg, Germany.
Proteomics Unit, Leibniz Institute for Experimental Virology (HPI), Martinistraße 52 (N63), D-20251 Hamburg, Germany.
Cells. 2022 Mar 11;11(6):959. doi: 10.3390/cells11060959.
The human skin and in particular its outermost layer, the epidermis, protects the body from potentially harmful substances, radiation as well as excessive water loss. However, the interference between the various stress responses of the epidermal keratinocytes, which often occur simultaneously, is largely unknown. The focus of this study was to investigate the interference between osmotic stress and DNA damage response. In addition to revealing the already well-described regulation of diverse gene sets, for example, cellular processes such as transcription, translation, and metabolic pathways (e.g., the KEGG citrate cycle and Reactome G2/M checkpoints), gene expression analysis of osmotically stressed keratinocytes revealed an influence on the transcription of genes also related to UV-induced DNA damage response. A gene network regulating the H2AX phosphorylation was identified to be regulated by osmotic stress. To analyze and test the interference between osmotic stress and DNA damage response, which can be triggered by UV stress on the one hand and oxidative stress on the other, in more detail, primary human keratinocytes were cultured under osmotic stress conditions and subsequently exposed to UV light and HO, respectively. γH2AX measurements revealed lower γH2AX levels in cells previously cultured under osmotic stress conditions.
人体皮肤，特别是其最外层表皮，可保护身体免受有害物质、辐射和过度水分流失的侵害。然而，表皮角质形成细胞的各种应激反应之间的相互干扰（这些反应通常同时发生）在很大程度上是未知的。本研究的重点是研究渗透胁迫与 DNA 损伤反应之间的干扰。除了揭示已经描述得很好的各种基因集的调节，例如细胞过程如转录、翻译和代谢途径（例如，KEGG 柠檬酸循环和 Reactome G2/M 检查点），渗透胁迫的角质形成细胞的基因表达分析显示对与 UV 诱导的 DNA 损伤反应相关的基因的转录也有影响。确定了一个调节 H2AX 磷酸化的基因网络受到渗透胁迫的调节。为了更详细地分析和测试渗透胁迫与 DNA 损伤反应之间的干扰，一方面可以由 UV 应激触发，另一方面可以由氧化应激触发，在渗透胁迫条件下培养原代人角质形成细胞，然后分别暴露于 UV 光和 HO。γH2AX 测量显示先前在渗透胁迫条件下培养的细胞中的 γH2AX 水平较低。
