Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/54586
Título: Cooperation of adenosine with macrophage toll-4 receptor agonists leads to increased glycolytic flux through the enhanced expression of PFKFB3 gene
Autores/as: Ruiz-García, Almudena
Monsalve, Eva
Novellasdemunt, Laura
Navarro-Sabaté, Áurea
Manzano, Anna
Rivero, Samuel
Castrillo Viguera, Antonio Jesús 
Casado, Marta
Laborda, Jorge
Bartrons, Ramón
Díaz-Guerra, María José M.
Palabras clave: Nf-Kappa-B
Hypoxia-Inducible Factor-1-Alpha
Activated Protein-Kinase
Tumor-Necrosis-Factor
Up-Regulation, et al.
Fecha de publicación: 2011
Editor/a: 0021-9258
Publicación seriada: Journal of Biological Chemistry 
Resumen: Macrophages activated through Toll receptor triggering increase the expression of the A(2A) and A(2B) adenosine receptors. In this study, we show that adenosine receptor activation enhances LPS-induced pfkfb3 expression, resulting in an increase of the key glycolytic allosteric regulator fructose 2,6-bisphosphate and the glycolytic flux. Using shRNA and differential expression of A(2A) and A(2B) receptors, we demonstrate that the A(2A) receptor mediates, in part, the induction of pfkfb3 by LPS, whereas the A(2B) receptor, with lower adenosine affinity, cooperates when high adenosine levels are present. pfkfb3 promoter sequence deletion analysis, site-directed mutagenesis, and inhibition by shRNAs demonstrated that HIF1 alpha is a key transcription factor driving pfkfb3 expression following macrophage activation by LPS, whereas synergic induction of pfkfb3 expression observed with the A(2) receptor agonists seems to depend on Sp1 activity. Furthermore, levels of phospho-AMP kinase also increase, arguing for increased PFKFB3 activity by phosphorylation in long term LPS-activated macrophages. Taken together, our results show that, in macrophages, endogenously generated adenosine cooperates with bacterial components to increase PFKFB3 isozyme activity, resulting in greater fructose 2,6-bisphosphate accumulation. This process enhances the glycolytic flux and favors ATP generation helping to develop and maintain the long term defensive and reparative functions of the macrophages.
URI: http://hdl.handle.net/10553/54586
ISSN: 0021-9258
DOI: 10.1074/jbc.M110.190298
Fuente: Journal of Biological Chemistry[ISSN 0021-9258],v. 286, p. 19247-19258
Colección:Artículos
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