ArticleCell death & disease2013
The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- The CaCell reports. Medicine · 2026Article
- Construction of diagnostic model and subtype analysis of major depressive disorder based on PANoptosis key genes.BMC psychiatry · 2025Article
- Synthesis of thiosemicarbazone derivatives and evaluation of their cytotoxicity with emphasis on ferroptosis biomarkers; anResearch in pharmaceutical sciences · 2025Article
- The Role of AMP-activated Protein Kinase in Oxytosis/Ferroptosis: Protector or Potentiator?Antioxidants & redox signaling · 2024Review
- Ferroptosis in health and disease.Redox biology · 2024Review
- IPAntioxidants (Basel, Switzerland) · 2024Article
- Ion channels in acinar cells in acute pancreatitis: crosstalk of calcium, iron, and copper signals.Frontiers in immunology · 2024Review
- Ferroptosis, Metabolic Rewiring, and Endometrial Cancer.International journal of molecular sciences · 2023Review
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes.International journal of molecular sciences · 2023Article
- Neuronal Store-Operated Calcium Channels.Molecular neurobiology · 2023Review
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- Ryanodine Receptor Mediated Calcium Release Contributes to Ferroptosis Induced in Primary Hippocampal Neurons by GPX4 Inhibition.Antioxidants (Basel, Switzerland) · 2023Article
- Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1.BMB reports · 2023Review
- A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine.Frontiers in neuroscience · 2023Review
- Organelle-Specific Mechanisms in Crosstalk between Apoptosis and Ferroptosis.Oxidative medicine and cellular longevity · 2023Review
- Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx.Journal of advanced research · 2022Article
- Internalized Amyloid-β (1-42) Peptide Inhibits the Store-Operated Calcium Entry in HT-22 Cells.International journal of molecular sciences · 2022Article
- Hypersensitivity to ferroptosis in chromophobe RCC is mediated by a glutathione metabolic dependency and cystine import via solute carrier family 7 member 11.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate-cystine antiporter system x(c)(-). GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT22 cells caused by downregulation of the Ca(2+) channel ORAI1, but not the Ca(2+) sensors STIM1 or STIM2. Pharmacological inhibition of SOCE mimicked this protection similarly to knockdown of ORAI1 by small interfering RNAs. Long-term calcium live-cell imaging after induction of the cell death program showed a specific reduction in Ca(2+)-positive cells by ORAI1 knockdown. These results suggest that dysregulated Ca(2+) entry through ORAI1 mediates the detrimental Ca(2+) entry in programmed cell death induced by GSH depletion. As this detrimental Ca(2+) influx occurs late in the course of the cell death program, it might be amenable to therapeutic intervention in diseases caused by oxidative stress.
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