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New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models

The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and sys...

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Autores principales: O’Brien, William G., Ling, Han Shawn, Zhao, Zhaoyang, Lee, Cheng Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528878/
https://www.ncbi.nlm.nih.gov/pubmed/28746349
http://dx.doi.org/10.1371/journal.pone.0180948
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author O’Brien, William G.
Ling, Han Shawn
Zhao, Zhaoyang
Lee, Cheng Chi
author_facet O’Brien, William G.
Ling, Han Shawn
Zhao, Zhaoyang
Lee, Cheng Chi
author_sort O’Brien, William G.
collection PubMed
description The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and systemic metabolism, we generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We have previously reported altered erythrocyte adenine nucleotide levels corresponding to altered oxygen saturation in mice deficient in both CD73 and AMPD3. Here we further investigate how these Ampd3(-/-)/Cd73(-/-) mice respond to the administered dose of AMP in comparison with the control models of single enzyme deficiency and wild type. We found that Ampd3(-/-)/Cd73(-/-) mice are more sensitive to AMP-induced hypometabolism than mice with a single enzyme deficiency, which are more sensitive than wild type. A dose-dependent rightward shift of erythrocyte p50 values in response to increasing amounts of extracellular AMP was observed. We provide further evidence for the direct uptake of AMP by erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake of AMP by the erythrocytes remained linear at the highest concentration tested, 10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but not by the other nucleotides and metabolites tested. Importantly, our studies suggest that AMP uptake is associated with an erythrocyte ATP release that is partially sensitive to inhibition by TRO19622 and Ca(++) ion. Taken together, our study suggests a novel mechanism by which erythrocytes recycle and maintain their adenine nucleotide pool through AMP uptake and ATP release.
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spelling pubmed-55288782017-08-07 New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models O’Brien, William G. Ling, Han Shawn Zhao, Zhaoyang Lee, Cheng Chi PLoS One Research Article The observation that induced torpor in non-hibernating mammals could result from an increased AMP concentration in circulation led our investigation to reveal that the added AMP altered oxygen transport of erythrocytes. To further study the effect of AMP in regulation of erythrocyte function and systemic metabolism, we generated mouse models deficient in key erythrocyte enzymes in AMP metabolism. We have previously reported altered erythrocyte adenine nucleotide levels corresponding to altered oxygen saturation in mice deficient in both CD73 and AMPD3. Here we further investigate how these Ampd3(-/-)/Cd73(-/-) mice respond to the administered dose of AMP in comparison with the control models of single enzyme deficiency and wild type. We found that Ampd3(-/-)/Cd73(-/-) mice are more sensitive to AMP-induced hypometabolism than mice with a single enzyme deficiency, which are more sensitive than wild type. A dose-dependent rightward shift of erythrocyte p50 values in response to increasing amounts of extracellular AMP was observed. We provide further evidence for the direct uptake of AMP by erythrocytes that is insensitive to dipyridamole, a blocker for ENT1. The uptake of AMP by the erythrocytes remained linear at the highest concentration tested, 10mM. We also observed competitive inhibition of AMP uptake by ATP and ADP but not by the other nucleotides and metabolites tested. Importantly, our studies suggest that AMP uptake is associated with an erythrocyte ATP release that is partially sensitive to inhibition by TRO19622 and Ca(++) ion. Taken together, our study suggests a novel mechanism by which erythrocytes recycle and maintain their adenine nucleotide pool through AMP uptake and ATP release. Public Library of Science 2017-07-26 /pmc/articles/PMC5528878/ /pubmed/28746349 http://dx.doi.org/10.1371/journal.pone.0180948 Text en © 2017 O’Brien et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
O’Brien, William G.
Ling, Han Shawn
Zhao, Zhaoyang
Lee, Cheng Chi
New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title_full New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title_fullStr New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title_full_unstemmed New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title_short New insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
title_sort new insights on the regulation of the adenine nucleotide pool of erythrocytes in mouse models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528878/
https://www.ncbi.nlm.nih.gov/pubmed/28746349
http://dx.doi.org/10.1371/journal.pone.0180948
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