title: Rapamycin regulates biochemical metabolites.
abstract: The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73(-/-) were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73(-/-) cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response.
authors.affiliation: Medical Research Council; Toxicology Unit; Leicester, UK; Department of Pharmacy, Health and Nutritional Sciences; University of Calabria; Rende, Cosenza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Porta
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Alexey
authors.initials: A
authors.lastname: Antonov
authors.forename: Alexander Vasilievich
authors.initials: AV
authors.lastname: Garabadgiu
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Anne E
authors.initials: AE
authors.lastname: Willis
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D008715:Methionine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D009687:Nuclear Proteins; C454920:delta Np73, mouse; D008715:Methionine; D005978:Glutathione; D020123:Sirolimus
keywords: MEF; autophagy; cell death; mTOR; metabolism; p53 family; p73; rapamycin