Aquaporins as channels for CO2, O2 and H2O2
Final Report Abstract
During the reporting period, the O2 permeability (PO2) of lipid membranes and the significance of aquaporin 1 (AQP1) and aquaporin 5 (AQP5) for O2 transport through cell membranes were investigated. PO2 of lipid membranes was determined for three different temperatures (7°C, 25°C, 35°C) and for membranes with different cholesterol contents (0 - 60%) using the stoppedflow technique. PO2 was found to be strongly dependent on the cholesterol content. For all three temperatures, the membranes could be categorised into two groups. Membranes with a low cholesterol content (0 - 20%) had a low PO2 (e.g. 0.03 cm/s at 35°C), membranes with a high cholesterol content (40 - 60%) had a PO2 that was an order of magnitude higher (e.g. 0.2 cm/s at 35°C). The significance of AQP1 for PO2 of cell membranes was investigated in stopped flow measurements on human erythrocytes and mouse erythrocytes. The permeability of human control erythrocytes and wildtype mouse erythrocytes was compared with the permeability of AQP1-deficient human erythrocytes and AQP1-KO-mouse erythrocytes at different temperatures. It was found that at high temperatures (25°C, 37°C) AQP1 makes no significant contribution to the PO2 of the erythrocyte membrane. At low temperatures of 7°C and 10°C, the permeability of AQP1-deficient erythrocytes is significantly reduced. These results show that AQP1 is an O2-channel in the erythrocyte membrane, but only plays a functional role at low temperatures. In a further part of the project, the maximum oxygen uptake (V̇ O2,max) of wild-type mice and AQP5-KO mice was determined using the Helox- method. The V̇O2,max in AQP5-KO mice was significantly reduced compared to wild-type mice under both normoxic and hypoxic conditions. Although AQP5 is expressed in the alveolar membrane of mice and represents a potential gas channel, no differences between wildtype and AQP1-KO mice could be found in further investigations of lung parameters such as diffusion capacity and arterial oxygen saturation. AQP5 therefore plays no functional role in O2 transport through the alveolar barrier. In further investigations, a reduced formation of brown adipose tissue under cold adaptation in AQP5-KO-mice was found to be the cause of the reduced V̇O2,max. The formation of brown adipose tissue or the conversion of white into brown adipose tissue is increased by AQP5.
Publications
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Cholesterin ist der wichtigste Regulator der CO2- Permeabilität biologischer Membranen. Atmungsphysiologische Arbeitstagung, Lübeck, 2019
Al-Samir S., Gros G. & Endeward V.
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Cholesterol – the major regulator of the CO2 permeability of biological membranes. Acta Physiologica, October 2019, Volume 227, Issue S719
Al-Samir S., Arias-Hidalgo M., Gros G. & Endeward V.
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CO2 permeability of the rat erythrocyte membrane and its inhibition. Journal of Enzyme Inhibition and Medicinal Chemistry, 36(1), 1601–1605.
Al-Samir, Samer; Prill, Maximilian; Supuran, Claudiu T.; Gros, Gerolf & Endeward, Volker
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O2 permeability of lipid bilayers is low, but increases with membrane cholesterol. Cellular and Molecular Life Sciences, 78(23), 7649-7662.
Al-Samir, Samer; Itel, Fabian; Hegermann, Jan; Gros, Gerolf; Tsiavaliaris, Georgios & Endeward, Volker
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Aqp5−/− mice exhibit reduced maximal body O2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 324(1), R109-R119.
Al-Samir, Samer; Yildirim, Ali Önder; Sidhaye, Venkataramana K.; King, Landon S.; Breves, Gerhard; Conlon, Thomas M.; Stoeger, Claudia; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabé de Angelis, Martin; Gros, Gerolf & Endeward, Volker
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O2 permeability of membranes. Symposium on gas transport, Aarhus, DK, 2024
Endeward V., Al-Samir S. & Gros G.
