Modulation of hydrogen peroxide-induced DNA damage, MAPKs activation and cell death in PC12 by ergothioneine
Abstract
Background & aims Ergothioneine (EGT) is a natural occurring compound, synthesized by soil bacteria in fungal substrates, exhibiting antioxidant functions in many cell models. The aim of this study was to assess the effect of EGT in the prevention of H2O2-dependent cell death and oxidative damage on a model of neural cell derived from rat pheocromocytoma, the PC12.Methods The ability of EGT was tested by the 3 (4,5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay and Comet assay. H2O2 insult was challenged with increasing concentration of antioxidant using two different incubation periods: 1 and 23 h of EGT pre-treatment followed by 23 and 1 h of H2O2, respectively, for both the MTT and the Comet assay data.Conclusion The pre-treatment for 23 h with EGT, 250 microM and 1mM, followed by 1h of H2O2 incubation at the concentration of 250 and 500 microM, resulted in increased cell viability (P < 0.001) compared to the H2O2 cell batch. This correlated with a decrease in DNA damage as visualized by the Comet assay. Moreover, protein analysis reveals that in the presence of 250 microM of H2O2, EGT acted as a p38-MAPK and Akt specific inhibitor. EGT may play a protective role in rescuing cells from stress-induced apoptosis, likely by activating an intracellular antioxidant pathway involving p38 MAPK genes cascade.
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Ergothioneine plays a role in survival signaling pathways, predominantly by stimulating phosphorylation of AKT/PKB signaling pathway in neuronal cells under mild, hydrogen peroxide-induced oxidative stress.
“Ergothioneine has been found to play a role in survival signaling pathways, predominantly by stimulating phosphorylation of AKT/PKB signaling pathway in neuronal cells under mild, hydrogen peroxide-induced oxidative stress (Colognato et al. 2006).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Colognato et al. 2006
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- Authors
- COLOGNATO, R., LAURENZA, I., FONTANA, I., COPPEDE, F., SICILIANO, G., COECKE, S., ARUOMA, O., BENZI, L., & MIGLIORE, L.
- Affiliations
- University of Pisa (IT)
- London South Bank University (GB)
- Joint Research Centre (IT)
- Corresponding author
- MIGLIORE, L
- Venue
- Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 25
- Issue
- 1
- Pages
- 135-145
- ISSN
- 0261-5614 (ISSN-L)
- OpenAlex
- W2049617130
- Cited by
- 81
- References
- 49
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- ergothioneine, hydrogen peroxide, oxidative DNA damage, PC12 cells, p38 MAPK, Akt, apoptosis, neuroprotection, antioxidants, cell viability, comet assay
- MeSH terms
- Animals, Antioxidants, Cell Survival, DNA Damage, Dose-Response Relationship, Drug, Ergothioneine, Hydrogen Peroxide, Oxidation-Reduction, Time Factors, Immunoblotting, PC12 Cells, Cell Death, Comet Assay, p38 Mitogen-Activated Protein Kinases, Rats
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