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A comprehensive characterization of the impact of mycophenolic acid on the metabolism of Jurkat T cells.

Abstract：

:Metabolic reprogramming is critical for T cell fate and polarization and is regulated by metabolic checkpoints, including Myc, HIF-1α, AMPK and mTORC1. Our objective was to determine the impact of mycophenolic acid (MPA) in comparison with rapamycin (Rapa), an inhibitor of mTORC1, on the metabolism of Jurkat T cells. We identified a drug-specific transcriptome signature consisting of the key enzymes and transporters involved in glycolysis, glutaminolysis or nucleotide synthesis. MPA produced an early and transient drop in the intracellular ATP content related to the inhibition of de novo synthesis of purines, leading to the activation of the energy sensor AMPK. MPA decreases glycolytic flux, consistent with a reduction in glucose uptake, but also in the oxidation of glutamine. Additionally, both drugs reduce aerobic glycolysis. The expression of HIF-1α and Myc, promoting the activation of glycolysis and glutaminolysis, was inhibited by MPA and Rapa. In conclusion, we report that MPA profoundly impacts the cellular metabolism of Jurkat T cells by generating an energetic distress, decreasing the glycolytic and glutaminolytic fluxes and by targeting HIF-1α and Myc. These findings open interesting perspectives for novel combinatorial therapeutic strategies targeting metabolic checkpoints to block the proliferation of T cells.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Fernández-Ramos AA,Marchetti-Laurent C,Poindessous V,Antonio S,Petitgas C,Ceballos-Picot I,Laurent-Puig P,Bortoli S,Loriot MA,Pallet N

doi

10.1038/s41598-017-10338-6

subject

Has Abstract

pub_date

2017-09-05 00:00:00

pages

10550

issue

1

issn

2045-2322

pii

10.1038/s41598-017-10338-6

journal_volume

7

pub_type

杂志文章

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