A novel role for NUPR1 in the keratinocyte stress response to UV oxidized phospholipids
Autor: | Florian Gruber, Valery N. Bochkov, Erwin Tschachler, Zhixu Ni, Julie Latreille, Maria Laggner, Johannes Grillari, Fernando J. Sialana, Marie-Sophie Narzt, Martin Bilban, Maria Fedorova, Ionela-Mariana Nagelreiter, Manuel Filzwieser, Olga Oskolkova, Michael Mildner, Gert Lubec |
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Rok vydání: | 2019 |
Předmět: |
Keratinocytes
0301 basic medicine Antioxidant Ultraviolet Rays medicine.medical_treatment Clinical Biochemistry Oxidative phosphorylation Models Biological Biochemistry Transcriptome 03 medical and health sciences 0302 clinical medicine Stress Physiological Physiology (medical) Basic Helix-Loop-Helix Transcription Factors Ultraviolet light medicine Humans Metabolomics lcsh:QH301-705.5 Phospholipids 030304 developmental biology chemistry.chemical_classification lcsh:R5-920 0303 health sciences Reactive oxygen species Gene Expression Profiling Organic Chemistry Lipid metabolism Lipid Metabolism Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation lcsh:Biology (General) chemistry Metabolome Unfolded protein response sense organs lcsh:Medicine (General) Keratinocyte Oxidation-Reduction 030217 neurology & neurosurgery Research Paper |
Zdroj: | Redox Biology, Vol 20, Iss, Pp 467-482 (2019) Redox Biology |
ISSN: | 2213-2317 |
Popis: | Ultraviolet light is the dominant environmental oxidative skin stressor and a major skin aging factor. We studied which oxidized phospholipid (OxPL) mediators would be generated in primary human keratinocytes (KC) upon exposure to ultraviolet A light (UVA) and investigated the contribution of OxPL to UVA responses. Mass spectrometric analysis immediately or 24 h post UV stress revealed significant changes in abundance of 173 and 84 lipid species, respectively. We identified known and novel lipid species including known bioactive and also potentially reactive carbonyl containing species. We found indication for selective metabolism and degradation of selected reactive lipids. Exposure to both UVA and to in vitro UVA - oxidized phospholipids activated, on transcriptome and proteome level, NRF2/antioxidant response signaling, lipid metabolizing enzyme expression and unfolded protein response (UPR) signaling. We identified NUPR1 as an upstream regulator of UVA/OxPL transcriptional stress responses and found this protein to be expressed in the epidermis. Silencing of NUPR1 resulted in augmented expression of antioxidant and lipid detoxification genes and disturbed the cell cycle, making it a potential key factor in skin reactive oxygen species (ROS) responses intimately involved in aging and pathology. Graphical abstract fx1 |
Databáze: | OpenAIRE |
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