Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts
| Autor: | Paulo J. Oliveira, Catarina Oliveira, Els M.A. van de Westerlo, Jori A. L. Wagenaars, Ricardo Amorim, Werner J.H. Koopman, Sofia Benfeito, Farhan Basit, Fernando Cagide, José A. Teixeira, Fernanda Borges, Peter H.G.M. Willems |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
HMOX1 NF-E2-Related Factor 2 SOD2 medicine.disease_cause Biochemistry Antioxidants Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) medicine Humans chemistry.chemical_classification Reactive oxygen species biology Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Glutathione Fibroblasts Molecular biology Mitochondria Heme oxygenase Oxidative Stress Cytosol Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] 030104 developmental biology chemistry biology.protein Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine, 163, pp. 314-324 Free Radical Biology and Medicine, 163, 314-324 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2020.12.023 |
| Popis: | Contains fulltext : 229055.pdf (Publisher’s version ) (Closed access) Phytochemical antioxidants like gallic and caffeic acid are constituents of the normal human diet that display beneficial health effects, potentially via activating stress response pathways. Using primary human skin fibroblasts (PHSFs) as a model, we here investigated whether such pathways were induced by novel mitochondria-targeted variants of gallic acid (AntiOxBEN(2)) and caffeic acid (AntiOxCIN(4)). Both molecules reduced cell viability with similar kinetics and potency (72 h incubation, IC50 ~23 μM). At a relatively high but non-toxic concentration (12.5 μM), AntiOxBEN(2) and AntiOxCIN(4) increased ROS levels (at 24 h), followed by a decline (at 72 h). Further analysis at the 72 h timepoint demonstrated that AntiOxBEN(2) and AntiOxCIN(4) did not alter mitochondrial membrane potential (Δψ), but increased cellular glutathione (GSH) levels, mitochondrial NAD(P)H autofluorescence, and mitochondrial superoxide dismutase 2 (SOD2) protein levels. In contrast, cytosolic SOD1 protein levels were not affected. AntiOxBEN(2) and AntiOxCIN(4) both stimulated the gene expression of Nuclear factor erythroid 2-related factor 2 (NRF2; a master regulator of the cellular antioxidant response toward oxidative stress). AntiOxBEN2 and ANtiOxCIN4 differentially affected the gene expression of the antioxidants Heme oxygenase 1 (HMOX1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1). Both antioxidants did not protect from cell death induced by GSH depletion and AntiOxBEN(2) (but not AntiOxCIN(4)) antagonized hydrogen peroxide-induced cell death. We conclude that AntiOxBEN(2) and AntiOxCIN(4) increase ROS levels, which stimulates NRF2 expression and, as a consequence, SOD2 and GSH levels. This highlights that AntiOxBEN(2) and AntiOxCIN(4) can act as prooxidants thereby activating endogenous ROS-protective pathways. |
| Databáze: | OpenAIRE |
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