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AMP Deaminase 3 Deficiency Enhanced 5′-AMP Induction of Hypometabolism

A hypometabolic state can be induced in mice by 5′-AMP administration. Previously we proposed that an underlying mechanism for this hypometabolism is linked to reduced erythrocyte oxygen transport function due to 5′-AMP uptake altering the cellular adenylate equilibrium. To test this hypothesis, we...

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Detalles Bibliográficos
Autores principales: Daniels, Isadora Susan, O′Brien, William G., Nath, Vinay, Zhao, Zhaoyang, Lee, Cheng Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774621/
https://www.ncbi.nlm.nih.gov/pubmed/24066180
http://dx.doi.org/10.1371/journal.pone.0075418
Descripción
Sumario:A hypometabolic state can be induced in mice by 5′-AMP administration. Previously we proposed that an underlying mechanism for this hypometabolism is linked to reduced erythrocyte oxygen transport function due to 5′-AMP uptake altering the cellular adenylate equilibrium. To test this hypothesis, we generated mice deficient in adenosine monophosphate deaminase 3 (AMPD3), the key catabolic enzyme for 5′-AMP in erythrocytes. Mice deficient in AMPD3 maintained AMPD activities in all tissues except erythrocytes. Developmentally and morphologically, the Ampd3(−/−) mice were indistinguishable from their wild type siblings. The levels of ATP, ADP but not 5′-AMP in erythrocytes of Ampd3(−/−) mice were significantly elevated. Fasting blood glucose levels of the Ampd3(−/−) mice were comparable to wild type siblings. In comparison to wild type mice, the Ampd3(−/−) mice displayed a deeper hypometabolism with a significantly delayed average arousal time in response to 5′-AMP administration. Together, these findings demonstrate a central role of AMPD3 in the regulation of 5′-AMP mediated hypometabolism and further implicate erythrocytes in this behavioral response.