ArticleMolecular brain2012
Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons.
Article in Molecular brain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Pooled it
- Glutathione Decreases Parkinsonism-Induced Ferroptosis and Oxidative Stress Through the Inhibition of the TRPM2 Channel in Neuronal Cells.Pharmacology research & perspectives · 2025Article
- Oxidant-Based Cytotoxic Agents During Aging: From Disturbed Energy Metabolism to Chronic Inflammation and Disease Progression.Biomolecules · 2025Review
- Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach.Cells · 2024Review
- Downregulation of TASK-3 Channel Induces Senescence in Granulosa Cells of Bovine Cystic Ovarian Follicles.International journal of molecular sciences · 2024Article
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- Functions of TRPs in retinal tissue in physiological and pathological conditions.Frontiers in molecular neuroscience · 2024Review
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
- Neuronal Senescence in the Aged Brain.Aging and disease · 2023Review
- Pathophysiological Roles of Transient Receptor Potential (Trp) Channels and Zinc Toxicity in Brain Disease.International journal of molecular sciences · 2023Review
- TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases.Frontiers in physiology · 2023Review
- ER-resident STIM1/2 couples CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Carvacrol protects the ARPE19 retinal pigment epithelial cells against high glucose-induced oxidative stress, apoptosis, and inflammation by suppressing the TRPM2 channel signaling pathways.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Article
- Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury.Neuron · 2022Article
- Role of TRPM2 in brain tumours and potential as a drug target.Acta pharmacologica Sinica · 2022Review
- Review
- Glutathione in Brain Disorders and Aging.Molecules (Basel, Switzerland) · 2022Review
- Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis.Molecular neurobiology · 2021Article
- Bevacizumab induces oxidative cytotoxicity and apoptosis via TRPM2 channel activation in retinal pigment epithelial cells: Protective role of glutathione.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Research progress on transient receptor potential melastatin 2 channel in nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlutathione (GSH) plays an important role in neuronal oxidant defence. Depletion of cellular GSH is observed in neurodegenerative diseases and thereby contributes to the associated oxidative stress and Ca2+ dysregulation. Whether depletion of cellular GSH, associated with neuronal senescence, directly influences Ca2+ permeation pathways is not known. Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. Importantly, GSH has been reported to inhibit TRPM2 channels, suggesting they may directly contribute to Ca2+ dysregulation associated with neuronal senescence. Herein, we explore the relation between cellular GSH and TRPM2 channel activity in long-term cultures of hippocampal neurons.
resultsIn whole-cell voltage-clamp recordings, we observe that TRPM2 current density increases in cultured pyramidal neurons over time in vitro. The observed increase in current density was prevented by treatment with NAC, a precursor to GSH synthesis. Conversely, treatment of cultures maintained for 2 weeks in vitro with L-BSO, which depletes GSH by inhibiting its synthesis, augments TRPM2 currents. Additionally, we demonstrate that GSH inhibits TRPM2 currents through a thiol-independent mechanism, and produces a 3.5-fold shift in the dose-response curve generated by ADPR, the intracellular agonist for TRPM2.
conclusionThese results indicate that GSH plays a physiologically relevant role in the regulation of TRPM2 currents in hippocampal pyramidal neurons. This interaction may play an important role in aging and neurological diseases associated with depletion of GSH.
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