Cell-cell contacts prevent t-BuOOH-triggered ferroptosis and cellular damage in vitro by regulation of intracellular calcium
Tert-butyl hydroperoxide (t-BuOOH) is an organic hydroperoxide widely used as a model compound to induce oxidative stress. It leads to a plethora of cellular damage, including lipid peroxidation, DNA double-strand breaks (DNA DSBs), and breakdown of the mitochondrial membrane potential (MMP). We cou...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2024
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| In: |
Archives of toxicology
Year: 2024, Jahrgang: 98, Heft: 9, Pages: 2953-2969 |
| ISSN: | 1432-0738 |
| DOI: | 10.1007/s00204-024-03792-5 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00204-024-03792-5 Verlag, kostenfrei, Volltext: https://link.springer.com/article/10.1007/s00204-024-03792-5 
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| Verfasserangaben: | Dagmar Faust, Christine Wenz, Stefanie Holm, Gregory Harms, Wolfgang Greffrath, Cornelia Dietrich |
| Zusammenfassung: | Tert-butyl hydroperoxide (t-BuOOH) is an organic hydroperoxide widely used as a model compound to induce oxidative stress. It leads to a plethora of cellular damage, including lipid peroxidation, DNA double-strand breaks (DNA DSBs), and breakdown of the mitochondrial membrane potential (MMP). We could show in several cell lines that t-BuOOH induces ferroptosis, triggered by iron-dependent lipid peroxidation. We have further revealed that not only t-BuOOH-mediated ferroptosis, but also DNA DSBs and loss of MMP are prevented by cell-cell contacts. The underlying mechanisms are not known. Here, we show in murine fibroblasts and a human colon carcinoma cell line that t-BuOOH (50 or 100 µM, resp.) causes an increase in intracellular Ca2+, and that this increase is key to lipid peroxidation and ferroptosis, DNA DSB formation and dissipation of the MMP. We further demonstrate that cell-cell contacts prevent t-BuOOH-mediated raise in intracellular Ca2+. Hence, we provide novel insights into the mechanism of t-BuOOH-triggered cellular damage including ferroptosis and propose a model in which cell-cell contacts control intracellular Ca2+ levels to prevent lipid peroxidation, DNA DSB-formation and loss of MMP. Since Ca2+ is a central player of toxicity in response to oxidative stress and is involved in various cell death pathways, our observations suggest a broad protective function of cell-cell contacts against a variety of exogenous toxicants. |
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| Beschreibung: | Online veröffentlicht: 30. Mai 2024 Gesehen am 13.11.2024 |
| Beschreibung: | Online Resource |
| ISSN: | 1432-0738 |
| DOI: | 10.1007/s00204-024-03792-5 |