Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia

Abstract

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accumulated fluid. To test whether hypoxia restricts cation transport in alveolar epithelial cells, cation uptake was measured in rat lung alveolar type II pneumocytes (AII cells) in primary culture and in A549 cells exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caused a[Formula: see text]-dependent inhibition of the Na-K pump, of Na-K-2Cl cotransport, and of total and amiloride-sensitive22Na uptake. Nifedipine failed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotransport occurred within ∼30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in cell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotransport flux after full activation with calyculin A, indicating a decreased transport capacity. [14C]serine incorporation into cell proteins was reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells, ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that hypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxia-induced reduction of transepithelial Na transport and water reabsorption by alveolar epithelium. If similar changes occur in vivo, the impaired cation transport across alveolar epithelial cells might contribute to the formation of hypoxic pulmonary edema.

Vibrio fischeri lux Genes Play an Important Role in Colonization and Development of the Host Light Organ

“…Hypoxia has been demonstrated to have an edemic effect on epithelial cells in other systems (18,25) and to result in exocytosis of cytoplasmic material (36). Such exocytosed material may be a source of nutrients to support the growing population of luminous symbiotic bacteria colonizing the crypt surfaces.…”

Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema

“…In alveolar type II cells, hypoxia (0% and 3% O 2 ) inhibits dome formation (292), decreases both amiloride-sensitive 22 Na influx and Na ϩ -K ϩ -ATPase activity, and decreases the amiloride-sensitive I sc (208,209,292,293,383), indicating that the transepithelial sodium transport is impaired. The mechanisms whereby hypoxia induces decreased sodium transport proteins activity depend on the severity and the length of hypoxic exposure.…”

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

“…Hypoxia causes time-and concentration-dependent decreases in ␣-, ␤-, and ␥-subunits of ENaC mRNA and decreases both ␤ 1 -and ␣ 1 -subunits of the Na ϩ -K ϩ -ATPase. Hypoxia itself also impairs cation transport in both A549 lung epithelial cells and rat alveolar cells (73). Oxidative inhibition of membrane Na ϩ -K ϩ -ATPase activity by H 2 O 2 produced as a result of hypoxia-reoxygenation may be an important mechanism leading to swelling and cytolysis (52).…”