Biochimica et biophysica acta. Molecular basis of disease, 2022-01, Vol.1868 (1), p.166287-166287, Article 166287
2022
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- Autor(en) / Beteiligte
- Titel
- NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury
- Ist Teil von
- Biochimica et biophysica acta. Molecular basis of disease, 2022-01, Vol.1868 (1), p.166287-166287, Article 166287
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2022
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Oxidative stress and lipid peroxidation are major causes of skin injury induced by ultraviolet (UV) irradiation. Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis. We generated UV irradiation-induced skin injury mice model to examine the accumulation of the lipid peroxides and iron. Lipid peroxides 4-HNE, the oxidative enzyme COX2, the oxidative DNA damage biomarker 8-OHdG, and the iron level were increased in UV irradiation-induced skin. The accumulation of iron and lipid peroxidation was also observed in UVB-irradiated epidermal keratinocytes without actual ongoing ferroptotic cell death. Ferroptosis was triggered in UV-irradiated keratinocytes stimulated with ferric ammonium citrate (FAC) to mimic the iron overload. Although GPX4 protected UVB-injured keratinocytes against ferroptotic cell death resulted from dysregulation of iron metabolism and the subsequent increase of lipid ROS, keratinocytes enduring constant UVB treatment were markedly sensitized to ferroptosis. Nicotinamide mononucleotide (NMN) which is a direct and potent NAD+ precursor supplement, rescued the imbalanced NAD+/NADH ratio, recruited the production of GSH and promoted resistance to lipid peroxidation in a GPX4-dependent manner. Taken together, our data suggest that NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced skin diseases or disorders. •UV irradiation induces the accumulation of lipid peroxides and iron overload in skin damage.•Keratinocytes show anti-ferroptosis phenomenon during UVB-induced injury.•NMN recruits GSH production and suppresses the accumulation of lipid peroxides via GPX4.•NMN and liproxstatin-1 strongly mitigate UV-induced skin injury.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0925-4439eISSN: 1879-260XDOI: 10.1016/j.bbadis.2021.166287Titel-ID: cdi_proquest_miscellaneous_2580691055
- Format
- –
- Schlagworte
- 8-Hydroxy-2'-Deoxyguanosine - pharmacology, Aldehydes - pharmacology, Animals, Cyclooxygenase 2 - genetics, DNA Damage - drug effects, DNA Damage - radiation effects, Ferric Compounds - pharmacology, Ferroptosis, Ferroptosis - drug effects, Ferroptosis - radiation effects, Glutathione - genetics, Humans, Iron - metabolism, Keratinocytes - drug effects, Keratinocytes - radiation effects, Lipid Peroxidation - drug effects, Lipid Peroxidation - radiation effects, Lipid Peroxides - pharmacology, Mice, Nicotinamide Mononucleotide - pharmacology, NMN, Oxidative Stress - drug effects, Oxidative Stress - genetics, Oxidative Stress - radiation effects, Phospholipid Hydroperoxide Glutathione Peroxidase - genetics, Quaternary Ammonium Compounds - pharmacology, Skin - drug effects, Skin - injuries, Skin - metabolism, Skin - pathology, Skin injury, Ultraviolet Rays - adverse effects