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TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A

Helga Simon-Molas1, Xavier Vallvé-Martínez1, Irene Caldera-Quevedo2

  • 1Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, C/Feixa Llarga, s/n, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.

International Journal of Molecular Sciences
|July 24, 2021
PubMed

Insights

TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) supports lymphocyte proliferation by fueling the pentose phosphate pathway. This glycolytic modulator is upregulated via the PI3K/AKT pathway in stimulated human lymphocytes.

Area of Science:

  • Cell Biology
  • Metabolic Regulation
  • Cancer Research

Background:

  • TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is implicated in cancer metabolism.
  • Its role in physiological proliferation, particularly in lymphocytes, is not well understood.

Purpose of the Study:

  • To investigate the function of TIGAR in primary human lymphocytes during mitotic stimulation.
  • To elucidate the signaling pathways regulating TIGAR expression and its metabolic consequences in proliferating lymphocytes.

Main Methods:

  • Primary human lymphocytes were stimulated with Concanavalin A (ConA).
  • TIGAR expression was analyzed using siRNA and pathway inhibitors (Akti-1/2, LY294002).
  • Proliferative markers (PCNA), reactive oxygen species (ROS), glucose 6-phosphate dehydrogenase (G6PDH) activity, and autophagy were assessed.

Main Results:

  • ConA stimulation induced TIGAR expression via the PI3K/AKT pathway.
  • TIGAR suppression decreased PCNA levels and increased cellular ROS.
  • TIGAR inhibition reduced G6PDH activity and elevated autophagy, indicating a role in pentose phosphate pathway (PPP) flux.

Conclusions:

  • TIGAR is upregulated in stimulated human lymphocytes through PI3K/AKT signaling.
  • TIGAR supports lymphocyte proliferation by directing carbon flux towards the PPP.
  • This study highlights TIGAR's role in lymphocyte metabolism and proliferation under physiological conditions.
Keywords:
PI3K/AKTPPPROSTIGARautophagyglycolysislymphocytes

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