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Shaheen, Seif O., PhD; Rutterford, Clare M., MSc; Lewis, Sarah J., PhD; Ring, Susan M., PhD; Holloway, John W., PhD; Golding, Jean, PhD; Henderson, A. John, MD
Journal of allergy and clinical immunology, 04/2015, Letnik: 135, Številka: 4Journal Article
Glutathione peroxidase (GPX) 4 is a unique membrane-associated selenium-dependent antioxidant enzyme that can directly reduce phospholipid hydroperoxides and protect against oxidative stress in mammalian cells.3 Aside from its antioxidant role, GPX4 has been implicated in lipoxygenase metabolism,4 which has major relevance to leukotriene synthesis and inflammatory signaling in asthma. ...demonstration of an interaction between selenium status and GPX4 genotype on asthma risk could strengthen the evidence for a causal role of selenium. Villette et al4 proposed that the rs713041 SNP in the 3' untranslated region of GPX4 may influence how efficiently selenocysteine is incorporated into GPX4, leading to altered GPX4 synthesis in response to variations in selenium supply.4 There is other evidence confirming that T/C variation (rs713041) has functional consequences,7 including a study showing that in individuals with the GPX4 (rs713041) TT genotype, oxidative stress decreased as in vivo selenium concentrations Furthermore, in vitro, selenium is necessary for the maximum expression of GPX4 in human lung epithelial cells.9 We therefore propose that low maternal blood selenium concentration leads to suboptimal GPX4 activity and impaired antioxidant defenses against oxidative stress in fetal airway epithelium, leading to epithelial damage, which, in turn, contributes to the pathogenesis of asthma.
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in: SICRIS
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