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Amino acid deprivation induces TXNIP expression by NRF2 downregulation

Se Hee Ahn1,2, Se-Kyeong Jang1, Yu Jin Kim1,2

  • 1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.

IUBMB Life
|December 6, 2023
PubMed

Insights

Amino acid restriction, particularly of arginine, glutamine, lysine, and methionine, increases thioredoxin-interacting protein (TXNIP) expression in lung cancer cells. This rise is linked to oxidative stress and NRF2 downregulation, suggesting a new cancer therapy target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Thioredoxin-interacting protein (TXNIP) is implicated in various diseases, including cancer and diabetes, and is sensitive to oxidative stress.
  • TXNIP is a potential therapeutic target, but its regulation under amino acid-restricted conditions remains unclear.

Purpose of the Study:

  • To investigate the regulation of TXNIP expression under amino acid (AA)-restricted conditions in non-small cell lung cancer (NSCLC) cells.
  • To explore the role of oxidative stress and key transcription factors in AA-deprivation-induced TXNIP expression.

Main Methods:

  • Cultured NSCLC cells under various AA deprivation conditions.
  • Assessed TXNIP expression levels.
  • Investigated the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and activating transcription factor 4 (ATF4).
  • Utilized N-acetyl-l-cysteine (NAC) to evaluate the role of reactive oxygen species (ROS).

Main Results:

  • AA deprivation, especially of arginine, glutamine, lysine, and methionine, significantly promoted TXNIP expression in NSCLC cells.
  • Increased TXNIP expression correlated with NRF2 downregulation, but not ATF4 activation.
  • NAC treatment suppressed TXNIP expression in AA-deprived cells, indicating ROS mediation.

Conclusions:

  • AA deprivation induces TXNIP expression in NSCLC cells, mediated by ROS production and NRF2 downregulation.
  • TXNIP regulation is linked to the redox homeostasis of AA metabolism.
  • AA restriction presents a potential therapeutic strategy for cancer treatment.
Keywords:
amino acid deprivationnon-small cell lung cancernuclear factor erythroid 2-related factor 2reactive oxygen speciesthioredoxin-interacting protein

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