A novel role for NUPR1 in the keratinocyte stress response to UV oxidized phospholipids.
Date
2019-01-01ICR Author
Author
Narzt, M-S
Nagelreiter, I-M
Oskolkova, O
Bochkov, VN
Latreille, J
Fedorova, M
Ni, Z
Sialana, FJ
Lubec, G
Filzwieser, M
Laggner, M
Bilban, M
Mildner, M
Tschachler, E
Grillari, J
Gruber, F
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Basic Helix-Loop-Helix Transcription Factors
Gene Expression Profiling
Gene Expression Regulation
Humans
Keratinocytes
Lipid Metabolism
Metabolome
Metabolomics
Models, Biological
Neoplasm Proteins
Oxidation-Reduction
Phospholipids
Stress, Physiological
Transcriptome
Ultraviolet Rays
Research team
Prote & Metabolomics Fac
Language
eng
Date accepted
2018-11-08
License start date
2019-01-01
Citation
Redox Biology, 2019, 20 pp. 467 - 482
Publisher
ELSEVIER