Published ahead of print on September 23, 2004, doi:10.1165/rcmb.2004-0202OC Am. J. Respir. Cell Mol. Biol., Volume 32, Number 1, January 2005, 44-51 A more recent version of this article appeared on January 1, 2005
Submitted on June 23, 2004 Hypoxia decreases cellular ATP-demand and inhibits mitochondrial respiration of A549 cellsKristin Heerlein1,1 Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany, 2 Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children's Hospital, Heidelberg, Germany * To whom correspondence should be addressed. E-mail: heimo.mairbaeurl{at}med.uni-heidelberg.de.
Hypoxia inhibits activity and expression of transporters involved in alveolar Na-reabsorption and fluid clearance. We studied whether this represents a mechanism to reduce energy consumption or whether it is the consequence of metabolic dysfunction. Oxygen consumption (JO2) of A549 cells and primary rat alveolar type II cells was measured by microrespirometry during normoxia, hypoxia (1.5% O2) and reoxygenation. In both cell types, acute and 24 h hypoxia decreased total JO2 significantly, reoxygenation restored JO2 after 5 min but not after 24 h hypoxia in A549 cells, whereas recovery was complete in type II cells. In A549 cells, normoxia Na/K-ATPase accounted for ~15% of JO2, Na/K-ATPase-related JO2 was decreased by ~25% in hypoxia. Inhibition of other ion transporters did not affect JO2. Protein synthesis related JO2 was not affected by acute hypoxia but after 24 h hypoxia (-30%). Acute and 24h hypoxia decreased JO2 of A549 cell mitochondrial complexes I, II and III 30 to 40%. Reoxygenation restored complex I activity after acute hypoxia but not after 24 h hypoxia. ATP was decreased (-30%) after 24 h hypoxia, lactate production rate was not affected. NADH was slightly elevated in acute hypoxia. Our findings indicate that inhibition of the Na/K-ATPase by hypoxia contributes little to energy preservation in hypoxia. It remains unclear to which extent hypoxic inhibition of mitochondrial metabolism affects ATP-consuming processes.
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