Abstract
Ultraviolet light is the dominant environmental oxidative skin stressor and a major factor in skin aging. We studied which oxidized phospholipid (OxPL) species 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 revealed dynamic UV-induced changes in abundance of 174 lipid species within 24 hours. We identified known and novel bioactive and also chemically reactive lipids and found indication for selective degradation of selected reactive lipid classes. 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 signaling. We further identified NUPR1 as an upstream regulator of UVA/OxPL transcriptional responses and found this protein expressed in the epidermis and permissive to modification by oxidized lipids. 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.
Highlights
The human skin is the organ most exposed to environmental oxidative assaults that cause cell damage, promote aging and result in pathologies
Throughout this study we compared the effects of ultraviolet A light (UVA) exposure on keratinocyte lipidome, transcriptome and proteome to the effects of externally addend UVA-oxidized phospholipids
We hypothesized that similar to what we observed in FB in keratinocytes UVAoxidized phospholipids would account for a part of the transcriptional UVA response
Summary
The human skin is the organ most exposed to environmental oxidative assaults that cause cell damage, promote aging and result in pathologies. The dominant extrinsic oxidizing factor is ultraviolet A light (UVA, 340–400 nm) which can penetrate deeply into the skin and modifies nucleic acids, proteins and lipids [74]. The UVA induced DNA damage is mutagenic and promotes photoaging [4], the premature aging phenotype of excessively sun exposed skin [67]. Reactive oxidized lipid species modify DNA and proteins such as histones [20] thereby affecting cell signaling and epigenetics [26]. Bi-reactive lipid oxidation products like bis-aldehydes crosslink macromolecules [65] which can be detected in photo-aged skin [46,79]. To the chemically reactive lipids, potent lipid signaling molecules are formed by UV through enzymes [43] or non-enzymatically
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call