Osmotic stress interferes with DNA damage response and H2AX phosphorylation in human keratinocytes

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 interplay between the various stress responses of the epidermal cells keratinocytes, which often occur simultaneously, is largely unknown. The focus of this study is to mechanistically investigate the interplay between osmotic stress and the UV-induced DNA damage response.In gene expression analysis of osmotically stressed keratinocytes compared to non-stressed keratinocytes, in addition to the already well-described regulation of diverse gene sets such as cellular processes like transcription, translation and metabolic pathways, an influence on the transcription of genes also related to the response to DNA damage by UV radiation was observed. To mechanistically analyze and test this interplay between osmotic stress and DNA damage response, which can be triggered by UV stress on the one hand and oxidative stress on the other hand, in more detail, primary human keratinocytes were cultured under osmotic stress conditions and subsequently exposed to UV light and H2O2, respectively. yH2AX measurements revealed lower yH2AX levels in cells previously cultured under osmotic stress conditions.