Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators

International Journal of Molecular Sciences

GladysO. Latunde-Dada¹  Naroa Kajarabille² 

[1] King’s College London, Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK;Nutrition and Obesity Group, Department of Nutrition and Food Sciences, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain;

关键词: ferroptosis;    antioxidants;    glutathione;    iron;   

DOI  :  10.3390/ijms20194968

来源: DOAJ

【 摘 要 】

Iron, the fourth most abundant element in the Earth’s crust, is vital in living organisms because of its diverse ligand-binding and electron-transfer properties. This ability of iron in the redox cycle as a ferrous ion enables it to react with H₂O₂, in the Fenton reaction, to produce a hydroxyl radical (•OH)—one of the reactive oxygen species (ROS) that cause deleterious oxidative damage to DNA, proteins, and membrane lipids. Ferroptosis is a non-apoptotic regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is triggered when the endogenous antioxidant status of the cell is compromised, leading to lipid ROS accumulation that is toxic and damaging to the membrane structure. Consequently, oxidative stress and the antioxidant levels of the cells are important modulators of lipid peroxidation that induce this novel form of cell death. Remedies capable of averting iron-dependent lipid peroxidation, therefore, are lipophilic antioxidants, including vitamin E, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1) and possibly potent bioactive polyphenols. Moreover, most of the enzymes and proteins that cascade or interact in the pathway of ferroptosis such as a subunit of the cystine/glutamate transporter x_c⁻ (SLC7A11), glutathione peroxidase 4 (GPX4), and the glutamate−cysteine ligase (GCLC) iron metabolism genes transferrin receptor 1 (TfR1) ferroportin, (Fpn) heme oxygenase 1 (HO-1) and ferritin are regulated by the antioxidant response element of the transcription factor, Nrf2. These, as well as other radical trapping antioxidants (RTAs), are discussed in the current review.

【 授权许可】

Unknown