O-2-induced ENaC expression is associated with NF-kappa B activation and blocked by superoxide scavenger AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Rafii, B., Tanswell, A. K., O'Tulakowski, G., Pitkanen, O., Belcastro-Taylor, R., O'Brodovich, H. 1998; 275 (4): L764-L770


Cultured rat fetal distal lung epithelial cells (FDLEs), when switched from fetal (3%) to postnatal (21%) O2 concentrations, have increased epithelial Na+ channel (ENaC) mRNA levels and amiloride-sensitive Na+ transport [O. Pitkänen, A. K. Tanswell, G. Downey, and H. O'Brodovich. Am. J. Physiol. 270 (Lung Cell. Mol. Physiol. 14): L1060-L1066, 1996]. The mechanisms by which O2 mediates these effects are unknown. After isolation, FDLEs were kept at 3% O2 overnight, then switched to 21% O2 (3-21% O2 group) or maintained at 3% O2 (3-3% O2 group) for 48 h. The amiloride-sensitive short-circuit current (Isc) in the 3-21% O2 group was double that in the 3-3% O2 group. Amiloride-sensitive Isc could not be induced by medium conditioned by 21% O2-exposed FDLEs but was reversed by returning the cells to 3% O2. Neither the cyclooxygenase inhibitor ibuprofen, liposome-encapsulated catalase, nor hydroperoxide scavengers (U-74389G or Trolox) blocked the O2-induced amiloride-sensitive Isc. In contrast, the cell-permeable superoxide scavenger tetramethylpiperidine-N-oxyl (TEMPO) eliminated the O2-induced increases in amiloride-sensitive Isc and ENaC mRNA levels. The switch from 3 to 21% O2 induced the transcription factor nuclear factor-kappaB, which could also be blocked by TEMPO. We conclude that 1) the O2-induced increase in amiloride-sensitive Isc is reversible and 2) the O2-induced increase in amiloride-sensitive Isc and ENaC mRNA levels is associated with activation of nuclear factor-kappaB and may be mediated, at least in part, by superoxide.

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