title: Metabolomics of the effect of AMPK activation by AICAR on human umbilical             vein endothelial cells.
abstract: AMP-activated protein kinase (AMPK) is a metabolic master switch expressed             in a great number of cells and tissues. AMPK is thought to modulate the cellular             response to different stresses that increase cellular AMP concentration. The adenosine             analog, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an AMPK             activator used in many studies to assess the effects of AMPK activation on cellular             metabolism and function. However, the effect of AICAR on cell metabolism reaches             many different pathways and metabolites, some of which do not seem to be fully             related to AMPK activation. We have now for the first time used NMR metabolomics             on human umbilical vein endothelial cells (HUVEC) for the study of the global             metabolic impact of AMPK activation by AICAR. In our study, incubation with AICAR             activates AMPK and is associated with, among others, broad metabolic alterations             in energy metabolism and phospholipid biosynthesis. Using NMR spectroscopy and             metabolic network tools, we analyzed the connections between the different metabolic             switches activated by AICAR. Our approach reveals a strong interconnection between             different phospholipid precursors and oxidation by-products. Metabolomics profiling             is a useful tool for detecting major metabolic alterations, generating new hypotheses             and provides some insight about the different molecular correlations in a complex             system. The present study shows that AICAR induces metabolic effects in cell metabolism             well beyond energy production pathways.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad                     de Valencia-CIBERehd, Valencia, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Martín
authors.forename: Ana
authors.initials: A
authors.lastname: Blas-García
authors.forename: Jose M
authors.initials: JM
authors.lastname: Morales
authors.forename: Miguel
authors.initials: M
authors.lastname: Marti-Cabrera
authors.forename: Daniel
authors.initials: D
authors.lastname: Monleón
authors.forename: Nadezda
authors.initials: N
authors.lastname: Apostolova
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D002478:Cells, Cultured; D002952:Citric Acid Cycle / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010743:Phospholipids / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology*
chemical_list: D010743:Phospholipids; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D055372:AMP-Activated Protein Kinases