ArticleAutophagy2012
Depletion of L-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes.
Article in Autophagy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
49 citing papers in PubMed, 86 citations in OpenAlex.
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- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Autophagy induced by metabolic processes leads to solid tumor cell metastatic dormancy and recurrence.Medical oncology (Northwood, London, England) · 2025Review
- Recent status and trends regarding oxidative stress in gliomas (2013 - 2025): a systematic review and bibliometric analysis.Frontiers in oncology · 2025Review
- Global Trends in Research of Amino Acid Metabolism in T Lymphocytes in Recent 15 Years: A Bibliometric Analysis.Journal of immunology research · 2025Article
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- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
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- Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies.Molecular cancer · 2023Review
- Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro.Microorganisms · 2023Article
- Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade.Nature communications · 2023Article
- Non-Essential Amino Acid Availability Influences Proteostasis and Breast Cancer Cell Survival During Proteotoxic Stress.Molecular cancer research : MCR · 2023Article
- ROS regulation in gliomas: implications for treatment strategies.Frontiers in immunology · 2023Review
- Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.Frontiers in immunology · 2023Review
- Tumor cell-derived asymmetric dimethylarginine regulates macrophage functions and polarization.Cancer cell international · 2022Article
- Plasma Polyamine Biomarker Panels: Agmatine in Support of Prostate Cancer Diagnosis.Biomolecules · 2022Article
- Review
- Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis.Frontiers in oncology · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L-arginine (L-Arg) deficiency results in decreased T-cell proliferation and impaired T-cell function. Here we have found that L-Arg depletion inhibited expression of different membrane antigens, including CD247 (CD3ζ), and led to an ER stress response, as well as cell cycle arrest at G(0)/G(1) in both human Jurkat and peripheral blood mitogen-activated T cells, without undergoing apoptosis. By genetic and biochemical approaches, we found that L-Arg depletion also induced autophagy. Deprivation of L-Arg induced EIF2S1 (eIF2α), MAPK8 (JNK), BCL2 (Bcl-2) phosphorylation, and displacement of BECN1 (Beclin 1) binding to BCL2, leading to autophagosome formation. Silencing of ERN1 (IRE1α) prevented the induction of autophagy as well as MAPK8 activation, BCL2 phosphorylation and XBP1 splicing, whereas led T lymphocytes to apoptosis under L-Arg starvation, suggesting that the ERN1-MAPK8 pathway plays a major role in the activation of autophagy following L-Arg depletion. Autophagy was required for survival of T lymphocytes in the absence of L-Arg, and resulted in a reversible process. Replenishment of L-Arg made T lymphocytes to regain the normal cell cycle profile and proliferate, whereas autophagy was inhibited. Inhibition of autophagy by ERN1, BECN1 and ATG7 silencing, or by pharmacological inhibitors, promoted cell death of T lymphocytes incubated in the absence of L-Arg. Our data indicate for the first time that depletion of L-Arg in T lymphocytes leads to a reversible response that preserves T lymphocytes through ER stress and autophagy, while remaining arrested at G(0)/G(1). Our data also show that the L-Arg depletion-induced ER stress response could lead to apoptosis when autophagy is blocked.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.