NF-kappaB blockade reduces the O2-evoked rise in Na+ conductance in fetal alveolar cells.
Electrophoretic mobility shift assays revealed minimal levels of NF-kappaB activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult alveolar (100 mmHg) P(O2), but revealed significant activation of this transcription factor in cells exposed to a rise in P(O2) mimicking that experienced at birth. This response was entirely abolished by pretreating cells with 5 mM sulfasalazine (SSA). This shift in P(O2) also evoked a rise in apical Na+ conductance (G(Na+)) that may underlie the O2-evoked stimulation of Na+ transport seen in these cells. Pretreatment with SSA had no effect upon G(Na+) in cells cultured continually at adult or fetal P(O2) but did inhibit the increase in G(Na+) seen in cells that had experienced the rise in P(O2). O2-evoked activation of NF-kappaB may thus mediate the increased Na+ transport that occurs when the distal lung epithelial cells are exposed to a physiologically-relevant increase in P(O2).
Haddad
J J
JJ
Lung Membrane Transport Group, Tayside Institute of Child Health, University of Dundee, Dundee, Scotland, DD1 9SY, United Kingdom.
Collett
A
A
Land
S C
SC
Olver
R E
RE
Wilson
S M
SM
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D008564:Membrane Potentials / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D012460:Sulfasalazine / Q000494:pharmacology
D016328:NF-kappa B; D015222:Sodium Channels; D012460:Sulfasalazine; D012964:Sodium; D010100:Oxygen