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Rapamycin regulates biochemical metabolites

Authors: TUCCI, PAOLA; Porta, G; AGOSTINI, MASSIMILIANO; Antonov, A; Garabadgiu, A; MELINO, GENNARO; Willis, A.;

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.

Countries
Italy, United Kingdom
Keywords

autophagy, 570, Sirolimus; cell death; Animals; Glutathione; metabolism; mTOR; Mice; Methionine; Mice, Knockout; p53 family; Metabolome; Nuclear Proteins; MEF; p73; Biosynthetic Pathways; Cells, Cultured; Pentose Phosphate Pathway; autophagy; rapamycin; Glycolysis, Cells, Knockout, p73, Pentose Phosphate Pathway, Mice, Methionine, Report, Animals, Sirolimu, Settore BIO/10 - BIOCHIMICA, Cells, Cultured, Nuclear Protein, Mice, Knockout, Sirolimus, MEF, Cultured, Animal, rapamycin, Nuclear Proteins, Biosynthetic Pathway, Glutathione, Biosynthetic Pathways, cell death, mTOR, Metabolome, p53 family, metabolism, Glycolysis

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    9
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Average
Average
Top 10%
Green
bronze