ArticleProceedings of the National Academy of Sciences of the United States of America2012
Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- A chemo-free thermo-sensitive necroptosis-inducing perfusate to enable potent hyperthermic intraperitoneal immunotherapy.National science review · 2026Article
- Involvement of interaction between TRPM2 and IKCA1 in temperature-dependent movement and IL-1β production in mouse microglia.The journal of physiological sciences : JPS · 2026Article
- Genetic inactivation of TRPM4 does not alter the temperature-dependent movement of mouse microglia.The journal of physiological sciences : JPS · 2026Article
- TRPV1 and TRPA1 channels exhibit bifurcated sensing of singlet oxygen and hydrogen peroxide.Redox biology · 2026Article
- Neuroimmune Regulation by TRPM2 Channels.Cells · 2026Review
- Tranilast Does Not Inhibit TRPV2.Cells · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPV2 Regulates Function of Human Neutrophil Granulocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- β-Glucan reprograms alveolar macrophages via neutrophil/IFNγ axis in a murine model of lung injury.eLife · 2025Article
- Heat Stress-Mediated Multi-Organ Injury: Pathophysiology and Treatment Strategies.Comprehensive Physiology · 2025Review
- Light-powered phagocytic macrophage microrobot (phagobot): both in vitro and in vivo.Light, science & applications · 2025Article
- Thermosensitive TRPM2: The regulatory mechanisms of its temperature sensitivity and physiological functions.The journal of physiological sciences : JPS · 2025Review
- TRP Channels in Excitotoxicity.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Direct Assessment of Temperature Sensitivity of the TRPM2 Channel with the Patch Clamp Technique.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature.Physiological reports · 2025Review
- Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma.Nature communications · 2024Article
- TRPV2: a universal regulator in cellular physiology with a yet poorly defined thermosensitivity.The journal of physiological sciences : JPS · 2024Review
- TRP Channels in Stroke.Neuroscience bulletin · 2024Review
- Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.Journal of translational medicine · 2024Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to sense temperature is essential for organism survival and efficient metabolism. Body temperatures profoundly affect many physiological functions, including immunity. Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca(2+)-permeable cation channel expressed in a wide range of immunocytes. TRPM2 is activated by adenosine diphosphate ribose and hydrogen peroxide (H(2)O(2)), although the activation mechanism by H(2)O(2) is not well understood. Here we report a unique activation mechanism in which H(2)O(2) lowers the temperature threshold for TRPM2 activation, termed "sensitization," through Met oxidation and adenosine diphosphate ribose production. This sensitization is completely abolished by a single mutation at Met-214, indicating that the temperature threshold of TRPM2 activation is regulated by redox signals that enable channel activity at physiological body temperatures. Loss of TRPM2 attenuates zymosan-evoked macrophage functions, including cytokine release and fever-enhanced phagocytic activity. These findings suggest that redox signals sensitize TRPM2 downstream of NADPH oxidase activity and make TRPM2 active at physiological body temperature, leading to increased cytosolic Ca(2+) concentrations. Our results suggest that TRPM2 sensitization plays important roles in macrophage functions.
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