α-Tocopherol Long-Chain Metabolite α-T-13'-COOH Exhibits Biphasic Effects on Cell Viability, Induces ROS-Dependent DNA Damage, and Modulates Redox Status in Murine RAW264.7 Macrophages.

Autor:	Liao S; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany., Börmel L; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany., Müller AK; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany., Gottschalk L; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Pritsch N; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Preisner LZ; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Samokhina O; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Schwarz M; Department of Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Kipp AP; Department of Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Schlörmann W; Department of Applied Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Glei M; Department of Applied Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany., Schubert M; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany., Schmölz L; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany.; Member of Leibniz Research Alliance, Leibniz Health Technology and Leibniz Centre for Photonics in Infection Research, Leibniz Institute of Photonic Technology, Jena, Germany., Wallert M; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany., Lorkowski S; Department of Nutritional Physiology and Biochemistry, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Germany.
Jazyk:	angličtina
Zdroj:	Molecular nutrition & food research [Mol Nutr Food Res] 2024 Nov 16, pp. e2400455. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1002/mnfr.202400455
Abstrakt:	Scope: The α-tocopherol long-chain metabolite α-tocopherol-13'-hydroxy-chromanol (α-T-13'-COOH) is a proposed regulatory intermediate of endogenous vitamin E metabolism. Effects of α-T-13'-COOH on cell viability and adaptive stress response are not well understood. The present study aims to investigate the concentration-dependent effects of α-T-13'-COOH on cellular redox homeostasis, genotoxicity, and cytotoxicity in murine RAW264.7 macrophages as a model system. Methods and Results: Murine RAW264.7 macrophages are exposed to various dosages of α-T-13'-COOH to determine its regulatory effects on reactive oxygen species (ROS) production, DNA damage, expression of stress-related markers, and the activity of ROS scavenging enzymes including superoxide dismutases, catalase, and glutathione-S-transferases. The impact on cell viability is assessed by analyzing cell proliferation, cell cycle arrest, and cell apoptosis. Conclusion: α-T-13'-COOH influences ROS production and induces DNA damage in a dose-dependent manner. The metabolite modulates the activity of ROS-scavenging enzymes, with significant changes observed in the activities of antioxidant enzymes. A biphasic response affecting cell viability is noted: sub-micromolar doses of α-T-13'-COOH promote cell proliferation and enhance DNA synthesis, whereas supraphysiological doses lead to DNA damage and cytotoxicity. It hypothesizes an adaptive stress response, characterized by upregulation of ROS detoxification mechanisms, enhanced cell cycle arrest, and increased apoptosis, indicating a correlation with oxidative stress and subsequent cellular damage. (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)
Databáze:	MEDLINE
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