title: Hypoxia decreases cellular ATP demand and inhibits mitochondrial respiration of a549 cells.
abstract: 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 approximately 15% of JO2, whereas Na/K-ATPase-related JO2 was decreased by approximately 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.
authors.affiliation: Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Heerlein
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hotz
authors.forename: Peter
authors.initials: P
authors.lastname: Bärtsch
authors.forename: Heimo
authors.initials: H
authors.lastname: Mairbäurl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase