Imaging of metabolic activity adaptations to UV stress, drugs and differentiation at cellular resolution in skin and skin equivalents - Implications for oxidative UV damage.
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
14
02
2020
revised:
12
05
2020
accepted:
13
05
2020
pubmed:
28
7
2020
medline:
25
5
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
The epidermis is a multi-layered epithelium that consists mainly of keratinocytes which proliferate in its basal layer and then differentiate to form the stratum corneum, the skin's ultimate barrier to the environment. During differentiation keratinocyte function, chemical composition, physical properties, metabolism and secretion are profoundly changed. Extrinsic or intrinsic stressors, like ultraviolet (UV) radiation thus may differently affect the epidermal keratinocytes, depending on differentiation stage. Exposure to UV elicits the DNA damage responses, activation of pathways which detoxify or repair damage or induction of programmed cell death when the damage was irreparable. Recently, rapid diversion of glucose flux into the pentose phosphate pathway (PPP) was discovered as additional mechanism by which cells rapidly generate reduction equivalents and precursors for nucleotides - both being in demand after UV damage. There is however little known about the correlation of such metabolic activity with differentiation state, cell damage and tissue localization of epidermal cells. We developed a method to correlate the activity of G6PD, the first and rate-limiting enzyme of this metabolic UV response, at cellular resolution to cell type, differentiation state, and cell damage in human skin and in organotypic reconstructed epidermis. We thereby could verify rapid activation of G6PD as an immediate UVB response not only in basal but also in differentiating epidermal keratinocytes and found increased activity in cells which initiated DNA damage responses. When keratinocytes had been UVB irradiated before organotypic culture, their distribution within the skin equivalent was abnormal and the G6PD activity was reduced compared to neighboring cells. Finally, we found that the anti-diabetic and potential anti-aging drug metformin strongly induced G6PD activity throughout reconstructed epidermis. Activation of the protective pentose phosphate pathway may be useful to enhance the skin's antioxidant defense systems and DNA damage repair capacity on demand.
Identifiants
pubmed: 32713735
pii: S2213-2317(20)30258-5
doi: 10.1016/j.redox.2020.101583
pmc: PMC7767734
pii:
doi:
Substances chimiques
Pharmaceutical Preparations
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101583Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
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