ArticleJournal of diabetes investigation2020
Nicotinic acetylcholine receptor signaling regulates inositol-requiring enzyme 1α activation to protect β-cells against terminal unfolded protein response under irremediable endoplasmic reticulum stress.
Article in Journal of diabetes investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
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- Rewired Neuroactive Ligand-Receptor Signaling Confers Adaptive Resistance to BCL-2 Inhibition in AML.Research square · 2026Article
- The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury.Cell stress & chaperones · 2025Article
- Xenobiotics Delivered by Electronic Nicotine Delivery Systems: Potential Cellular and Molecular Mechanisms on the Pathogenesis of Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- Living Dangerously: Protective and Harmful ER Stress Responses in Pancreatic β-Cells.Diabetes · 2021Review
- Article
- Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome.Inflammation · 2021Review
- Therapeutic potential of α7 nicotinic acetylcholine receptor agonists to combat obesity, diabetes, and inflammation.Reviews in endocrine & metabolic disorders · 2020Review
- Targeting Adaptive IRE1α Signaling and PLK2 in Multiple Myeloma: Possible Anti-Tumor Mechanisms of KIRA8 and Nilotinib.International journal of molecular sciences · 2020Observational
- Nicotinic acetylcholine receptor signaling regulates inositol-requiring enzyme 1α activation to protect β-cells against terminal unfolded protein response under irremediable endoplasmic reticulum stress.Journal of diabetes investigation · 2020Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
AIMS/
introductionUnder irremediable endoplasmic reticulum (ER) stress, hyperactivated inositol-requiring enzyme 1α (IRE1α) triggers the terminal unfolded protein response (T-UPR), causing crucial cell dysfunction and apoptosis. We hypothesized that nicotinic acetylcholine receptor (nAChR) signaling regulates IRE1α activation to protect β-cells from the T-UPR under ER stress. MATERIALS AND
methodsThe effects of nicotine on IRE1α activation and key T-UPR markers, thioredoxin-interacting protein and insulin/proinsulin, were analyzed by real-time polymerase chain reaction and western blotting in rat INS-1 and human EndoC-βH1 β-cell lines. Doxycycline-inducible IRE1α overexpression or ER stress agents were used to induce IRE1α activation. An α7 subunit-specific nAChR agonist (PNU-282987) and small interfering ribonucleic acid for α7 subunit-specific nAChR were used to modulate nAChR signaling.
resultsNicotine inhibits the increase in thioredoxin-interacting protein and the decrease in insulin 1/proinsulin expression levels induced by either forced IRE1α hyperactivation or ER stress agents. Nicotine attenuated X-box-binding protein-1 messenger ribonucleic acid site-specific splicing and IRE1α autophosphorylation induced by ER stress. Furthermore, PNU-282987 attenuated T-UPR induction by either forced IRE1α activation or ER stress agents. The effects of nicotine on attenuating thioredoxin-interacting protein and preserving insulin 1 expression levels were attenuated by pharmacological and genetic inhibition of α7 nAChR. Finally, nicotine suppressed apoptosis induced by either forced IRE1α activation or ER stress agents.
conclusionsOur findings suggest that nAChR signaling regulates IRE1α activation to protect β-cells from the T-UPR and apoptosis under ER stress partly through α7 nAChR. Targeting nAChR signaling to inhibit the T-UPR cascade may therefore hold therapeutic promise by thwarting β-cell death in diabetes.
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