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
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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