Hypoxic activation of an amiloride-sensitive cation conductance in alveolar epithelial cells.
Imposing hypoxia (P(O(2)) = 23 mmHg) upon A549 cells elicited increased G(amil) although previous work had predicted a fall in this parameter. G(amil) appeared to be dependent upon glucocorticoid-driven gene expression, a process inhibited by ERK, an enzyme activated by oxidative stress. However, hypoxia transiently activated this enzyme and the response was blocked by glucocorticoids, showing that the rise in G(amil) occurs only if ERK activation is suppressed. Fluorimetric assays showed that lowering P(O(2)) elicited H(2)O(2) formation indicating that this maneuver actually imposes oxidative stress, thus explaining how hypoxia can elicit responses normally associated with a rise in P(O(2)).
Jovanovic
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Lung Membrane Transport Group, Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY, United Kingdom.
Land
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SC
Olver
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Wilson
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SM
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004553:Electric Conductivity; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D017136:Ion Transport; D015735:Mifepristone / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000502:physiology; D011312:Pressure; D011650:Pulmonary Alveoli / Q000166:cytology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D000584:Amiloride; D003907:Dexamethasone; D012964:Sodium; D006861:Hydrogen Peroxide; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen