Osmotic Stress Interferes with DNA Damage Response and H2AX Phosphorylation in Human Keratinocytes

被引:4
作者
Hoen, Laura [1 ]
Rudisch, Christoph [1 ]
Wick, Michael [1 ]
Indenbirken, Daniela [2 ]
Grundhoff, Adam [2 ]
Wegwitz, Florian [3 ]
Kalkhof, Stefan [1 ,4 ]
Hildebrand, Janosch [1 ]
机构
[1] Coburg Univ Appl Sci & Arts Coburg, Inst Bioanal, Friedrich Streib Str 2, D-96450 Coburg, Germany
[2] Leibniz Inst Expt Virol HPI, Prote Unit, Martinistr 52,N63, D-20251 Hamburg, Germany
[3] Univ Med Ctr Gottingen, Dept Gynecol & Obstet, Robert Koch Str 40, D-37075 Gottingen, Germany
[4] Fraunhofer Inst Cell Therapy & Immunol, Perlickstr 1, D-04103 Leipzig, Germany
关键词
keratinocytes; UV radiation; gene regulation; DNA repair disorders; osmotic stress; HISTONE H2AX; HYDROGEN-PEROXIDE; HYPERTONIC STRESS; HIGH NACL; CELLS; SKIN; CHECKPOINT; ATR; GAMMA-H2AX; ACTIVATION;
D O I
10.3390/cells11060959
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 H2O2, respectively. gamma H2AX measurements revealed lower gamma H2AX levels in cells previously cultured under osmotic stress conditions.
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页数:12
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