Glutathione-dependent and -independent oxidative stress-control mechanisms distinguish normal human mammary epithelial cell subsets
| Autor: | Connie J. Eaves, Maisam Makarem, Long V. Nguyen, Nagarajan Kannan, Afshin Raouf, Peter Eirew, Kingsley Shih, Yifei Dong, Joanne T. Emerman |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Antioxidant
medicine.medical_treatment Blotting Western Oxidative phosphorylation medicine.disease_cause Real-Time Polymerase Chain Reaction Superoxide dismutase chemistry.chemical_compound Oxygen Consumption medicine Humans Progenitor cell Mammary Glands Human chemistry.chemical_classification Reactive oxygen species Multidisciplinary biology Stem Cells Epithelial Cells Glutathione Biological Sciences Flow Cytometry Cell biology Oxidative Stress chemistry Immunology biology.protein Peroxiredoxin Reactive Oxygen Species Oxidative stress DNA Damage |
| Popis: | Mechanisms that control the levels and activities of reactive oxygen species (ROS) in normal human mammary cells are poorly understood. We show that purified normal human basal mammary epithelial cells maintain low levels of ROS primarily by a glutathione-dependent but inefficient antioxidant mechanism that uses mitochondrial glutathione peroxidase 2. In contrast, the matching purified luminal progenitor cells contain higher levels of ROS, multiple glutathione-independent antioxidants and oxidative nucleotide damage-controlling proteins and consume O2 at a higher rate. The luminal progenitor cells are more resistant to glutathione depletion than the basal cells, including those with in vivo and in vitro proliferation and differentiation activity. The luminal progenitors also are more resistant to H2O2 or ionizing radiation. Importantly, even freshly isolated "steady-state" normal luminal progenitors show elevated levels of unrepaired oxidative DNA damage. Distinct ROS control mechanisms operating in different subsets of normal human mammary cells could have differentiation state-specific functions and long-term consequences. |
| Databáze: | OpenAIRE |
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