Adaptive Antioxidant Response Protects Dermal Fibroblasts from UVA-Induced Phototoxicity
Abstract
In response to the attack of reactive oxygen species (ROS) produced upon UV irradiation, the skin has developed a complex antioxidant defense system. Here we report that, in addition to the previously published induction of manganese superoxide dismutase (MnSOD) activity, single and, to a higher extent, repetitive low-dose UVA irradiation also leads to a substantial upregulation of glutathione peroxidase (GPx) activity. This concomitant adaptive response of two antioxidant enzymes acting in the same detoxification pathway coincided with the protection from high-UVA-dose-induced cytotoxicity conferred by low-dose UVA preirradiation. Whereas an interval of 24 h did not, an interval of 12 h did lead to the induction of MnSOD activity and, under selenium-supplemented conditions, of GPx activity as well, conferring definite cellular protection from UVA-induced phototoxicity. Moreover, under selenium-deficient conditions, which abrogate the UVA-mediated induction of GPx activity, adaptive protection against the cytotoxic effects of high UVA doses was significantly lower compared with selenium supplementation. Isolated 4.6-fold overexpression of MnSOD activity in stably transfected fibroblasts led to specific resistance from UVA-mediated phototoxicity under selenium-deficient conditions. Collectively, these data indicate that the concomitant induction of MnSOD and GPx activity is related to the optimal adaptive protection from photooxidative damage. This adaptive antioxidant protection clearly depends on the irradiation interval and a sufficient selenium concentration, findings that may have important implications for the improvement of photoprotective and phototherapeutic strategies in medicine.
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Upregulation of SOD2 is induced in the senescent phenotype in a paracrine way by physical insults such as UV irradiation or by immune release of chemokines, soluble factors, and cytokines from keratinocytes.
“The upregulation of SOD2 is induced in the senescent phenotype also in a paracrine way by physical insults such as UV irradiation [39] or by the immune release of chemokines, soluble factors, and cytokines from keratinocytes [40].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [39]
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- Authors
- Meewes, C., Brenneisen, P., Wenk, J., Kuhr, L., Ma, W., Alikoski, J., Poswig, A., Krieg, T., & Scharffetter-Kochanek, K.
- Affiliations
- University of Cologne (DE)
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 30
- Issue
- 3
- Pages
- 238-247
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W1971130793
- Cited by
- 98
- References
- 46
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität zu Köln
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- dermal fibroblasts, manganese superoxide dismutase, glutathione peroxidase, selenium, reactive oxygen species, photooxidative damage, photoprotection, skin
- MeSH terms
- Antioxidants, Cells, Cultured, Child, Child, Preschool, Dose-Response Relationship, Radiation, Enzyme Induction, Fibroblasts, Glutathione Peroxidase, Humans, Selenium, Skin, Superoxide Dismutase, Transfection, Ultraviolet Rays, Gene Expression, Cell Death
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