This Article Full Text Full Text (PDF) All Versions of this Article: 2004-0202OCv1 32/1/44    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heerlein, K. Articles by Mairbäurl, H. Search for Related Content PubMed PubMed Citation Articles by Heerlein, K. Articles by Mairbäurl, H.

Hypoxia Decreases Cellular ATP Demand and Inhibits Mitochondrial Respiration of A549 Cells

Medical Clinic VII, Sports Medicine, University of Heidelberg; and Division of Metabolic and Endocrine Diseases, Department of General Pediatrics, University Children's Hospital, Heidelberg, Germany

Correspondence and requests for reprints should be addressed to Heimo Mairbäurl, Medical Clinic VII, Sports Medicine, University of Heidelberg, INF 410, 69120 Heidelberg, Germany. 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 for reducing 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 and reoxygenation restored JO₂ after 5 min but not after 24 h of hypoxia in A549 cells, whereas recovery was complete in type II cells. In A549 cells under normoxia Na/K-ATPase accounted for 15% of JO₂, whereas 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 decreased by 30% after 24-h hypoxia. Acute and 24-h hypoxia decreased JO₂ of A549 cell mitochondrial complexes I, II, and III by 30–40%. Reoxygenation restored complex I activity after acute hypoxia but not after 24-h hypoxia. ATP was decreased 30% after 24-h hypoxia, but lactate production rate was not affected. Reduced nicotinamine adenine dinucleotide 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 what extent hypoxic inhibition of mitochondrial metabolism affects ATP-consuming processes.

Key Words: energy metabolism • hypoxia • mitochondrial electron transfer chain • Na-transport • respirometry

This article has been cited by other articles:

				I. O. Kurochkin, A. V. Ivanina, S. Eilers, C. A. Downs, L. A. May, and I. M. Sokolova Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica) Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1262 - R1272. [Abstract] [Full Text] [PDF]

				C. Clerici and C. Planes Gene regulation in the adaptive process to hypoxia in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L267 - L274. [Abstract] [Full Text] [PDF]

				S. Guney, A. Schuler, A. Ott, S. Hoschele, S. Zugel, E. Baloglu, P. Bartsch, and H. Mairbaurl Dexamethasone prevents transport inhibition by hypoxia in rat lung and alveolar epithelial cells by stimulating activity and expression of Na+-K+-ATPase and epithelial Na+ channels Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1332 - L1338. [Abstract] [Full Text] [PDF]

				F. A. Groenman, M. Rutter, J. Wang, I. Caniggia, D. Tibboel, and M. Post Effect of chemical stabilizers of hypoxia-inducible factors on early lung development Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L557 - L567. [Abstract] [Full Text] [PDF]

				E. Rissanen, H. K. Tranberg, and M. Nikinmaa Oxygen availability regulates metabolism and gene expression in trout hepatocyte cultures Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1507 - R1515. [Abstract] [Full Text] [PDF]

				M. Jain and J. I. Sznajder Effects of Hypoxia on the Alveolar Epithelium Proceedings of the ATS, October 1, 2005; 2(3): 202 - 205. [Abstract] [Full Text] [PDF]