Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kannan N,Nguyen LV,Makarem M,Dong Y,Shih K,Eirew P,Raouf A,Emerman JT,Eaves CJdoi
10.1073/pnas.1403813111subject
Has Abstractpub_date
2014-05-27 00:00:00pages
7789-94issue
21eissn
0027-8424issn
1091-6490pii
1403813111journal_volume
111pub_type
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