Oxidized Ferric and Ferryl Forms of Hemoglobin Trigger Mitochondrial Dysfunction and Injury in Alveolar Type I Cells

作者: Narendranath Reddy Chintagari , Sirsendu Jana , Abdu I. Alayash

DOI: 10.1165/RCMB.2015-0197OC

关键词: Heme oxygenaseHemoglobinMolecular biologyBiochemistryDepolarizationRedoxHemeHemopexinCell cultureMitochondrionChemistry

摘要: Lung alveoli are lined by alveolar type (AT) 1 cells and cuboidal AT2 cells. The AT1 likely to be exposed cell-free hemoglobin (Hb) in multiple lung diseases; however, the role of Hb redox (reduction-oxidation) reactions their precise contributions cell injury not well understood. Using mouse epithelial (E10) as an model, we demonstrate here that higher oxidation states, ferric (HbFe(3+)) ferryl (HbFe(4+)) subsequent heme loss play a central genesis injury. Exposures HbFe(2+) HbFe(3+) for 24 hours induced expression oxygenase (HO)-1 protein E10 HO-1 translocation purified mitochondrial fractions. Both these effects were intensified with increasing states Hb. Next, examined free on bioenergetic function measuring changes transmembrane potential oxygen consumption rate. In contrast HbFe(2+), reduced basal rate, indicating compromised activity. However, HbFe(4+) exposure only early but also caused dysfunction within 12 when compared HbFe(3+). Exposure depolarization deleterious reversed addition scavenger proteins, haptoglobin hemopexin. Collectively, data establish, first time, injury, mediated through transition states.

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