ArticleCell calcium2022
The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells.
Article in Cell calcium, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Cigarette Smoke Exposure Attenuates T2R-Mediated Apoptosis in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- Mechanisms of Mitochondrial Toxicity and Cytotoxicity Caused by Pseudomonas aeruginosa Pyocyanin in Human Nasal Epithelial Cells.International forum of allergy & rhinology · 2026Article
- T2R5 Agonist Phendione Decreases Cell Viability and Induces Apoptosis in Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2026Article
- Opposite Effects of Diacylglycerol and Phosphatidic Acid in the Modulation of the Plasma Membrane CaBiomedicines · 2026Article
- Respiratory Ciliary Beat Frequency in COPD: Balancing Oxidative Stress and Pharmacological Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Bitter Taste Receptors in Bacterial Infections and Innate Immunity.Immunity, inflammation and disease · 2025Review
- Investigating laryngeal squamous cell carcinoma: clinical features and the role of TAS2R16 polymorphisms and its protein levels.Discover oncology · 2025Article
- A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Hops bitter β-acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction.International forum of allergy & rhinology · 2025Article
- Novel therapeutic strategy: Nrf2 activation in targeting senescence-related changes in chronic obstructive pulmonary disease.Journal of thoracic disease · 2025Article
- Extragustatory bitter taste receptors in head and neck health and disease.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro.International forum of allergy & rhinology · 2024Article
- Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.Cell reports · 2023Article
- Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced CaCell death discovery · 2023Article
- Interkingdom Detection of Bacterial Quorum-Sensing Molecules by Mammalian Taste Receptors.Microorganisms · 2023Review
- Utilizing the Off-Target Effects of T1R3 Antagonist Lactisole to Enhance Nitric Oxide Production in Basal Airway Epithelial Cells.Nutrients · 2023Article
- Savory Signaling: T1R Umami Receptor Modulates Endoplasmic Reticulum Calcium Store Content and Release Dynamics in Airway Epithelial Cells.Nutrients · 2023Article
- Loss of CFTR function is associated with reduced bitter taste receptor-stimulated nitric oxide innate immune responses in nasal epithelial cells and macrophages.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules. Activation of cilia T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by loss of motile cilia and/or squamous metaplasia. To understand T2R function within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells. Several T2Rs localize to the nucleus in de-differentiated cells that typically localize to cilia in differentiated cells. As cilia and nuclear import utilize shared proteins, some T2Rs may target to the nucleus in the absence of motile cilia. T2R agonists selectively elevated nuclear and mitochondrial calcium through a G-protein-coupled receptor phospholipase C mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.
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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.