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Updated: Jul 31, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the

Qian-Lin Tan1, Ming-Xia Zhang1, Deng-Hu Yao1

  • 1Department of Nephrology, Minda Hospital Affiliated to Hubei Minzu University, Hubei Clinical Research Center for Kidney Disease, Enshi, PR China.

Nutrition and Cancer
|May 4, 2023
PubMed

Insights

TP53-induced glycolysis and apoptosis regulator (TIGAR) protects against kidney cell ferroptosis by activating the mTOR/S6KP70 pathway. This finding suggests TIGAR activation may treat crystal-induced kidney diseases.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Nephrology

Background:

  • TP53-induced glycolysis and apoptosis regulator (TIGAR) is implicated in nephropathy, but its precise role in ferroptosis remains unclear.
  • Understanding TIGAR's mechanism is crucial for developing treatments for kidney diseases.

Purpose of the Study:

  • To investigate the biological significance of TIGAR in adenine-induced ferroptosis in human proximal tubular epithelial (HK-2) cells.
  • To elucidate the underlying molecular mechanism by which TIGAR modulates ferroptosis.

Main Methods:

  • HK-2 cells with altered TIGAR expression were exposed to adenine to induce ferroptosis.
  • Assays for reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were performed.
  • Quantitative real-time-PCR and western blotting assessed ferroptosis markers (SLC7A11, GPX4) and mTOR/S6KP70 pathway activation.

Main Results:

  • Adenine induced ferroptosis in HK-2 cells, indicated by altered levels of GSH, SLC7A11, GPX4, iron, MDA, and ROS.
  • TIGAR overexpression suppressed ferroptosis and activated the mTOR/S6KP70 signaling pathway.
  • Inhibiting mTOR or S6KP70 diminished TIGAR's protective effect against ferroptosis.

Conclusions:

  • TIGAR inhibits adenine-induced ferroptosis in HK-2 cells by activating the mTOR/S6KP70 signaling pathway.
  • Targeting the TIGAR/mTOR/S6KP70 axis presents a potential therapeutic strategy for crystal nephropathies.

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