ArticleJournal of neuroinflammation2016
STIMs and Orai1 regulate cytokine production in spinal astrocytes.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.Frontiers in neuroscience · 2026Article
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- Store-Operated Calcium Channels in the Nervous System.Annual review of physiology · 2025Review
- Calcium signaling at the interface between astrocytes and brain inflammation.Current opinion in neurobiology · 2025Review
- H3K27 Trimethylation-Mediated Downregulation of miR-216a-3p in Sensory Neurons Regulates Neuropathic Pain Behaviors via Targeting STIM1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Novel insights into STIM1's role in store-operated calcium entry and its implications for T-cell mediated inflammation in trigeminal neuralgia.Frontiers in molecular neuroscience · 2024Article
- Astrocyte-specific CaBiochemistry and cell biology = Biochimie et biologie cellulaire · 2023Review
- Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels.Nature communications · 2023Article
- Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury.Neural regeneration research · 2023Article
- SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Toll-like receptor 4 activation enhances Orai1-mediated calcium signal promoting cytokine production in spinal astrocytes.Cell calcium · 2022Article
- Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGFCancers · 2021Article
- Xist attenuates acute inflammatory response by female cells.Cellular and molecular life sciences : CMLS · 2021Article
- Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.Frontiers in cell and developmental biology · 2021Article
- Store-Operated Calcium Channels Contribute to Remifentanil-Induced Postoperative Hyperalgesia via Phosphorylation of CaMKIIα in Rats.Journal of pain research · 2021Article
- mtROS InducedFrontiers in immunology · 2021Article
- Cell-wide mapping of Orai1 channel activity reveals functional heterogeneity in STIM1-Orai1 puncta.The Journal of general physiology · 2020Article
- Kidins220/ARMS controls astrocyte calcium signaling and neuron-astrocyte communication.Cell death and differentiation · 2020Article
- Reactive oxygen species play a role in P2X7 receptor-mediated IL-6 production in spinal astrocytes.Purinergic signalling · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOur previous study demonstrated that a store-operated calcium channel (SOCC) inhibitor (YM-58483) has central analgesic effects. However, the cellular and molecular mechanisms of such effects remain to be determined. It is well-known that glial cells play important roles in central sensitization. SOC entry (SOCE) has been implicated in many cell types including cortical astrocytes. However, the role of the SOCC family in the function of astrocytes has not been determined. Here, we thoroughly investigated the expression and the functional significance of SOCCs in spinal astrocytes.
methodsPrimary cultured astrocytes were prepared from neonatal (P2-P3) CD1 mice. Expressions of mRNAs and proteins were respectively assessed by real-time PCR and Western blot analysis. SOCE was measured using a calcium imaging system. Live-cell STIM1 translocation was detected using a confocal microscope. Cytokine levels were measured by the enzyme-linked immunosorbent assay.
resultsWe found that the SOCC family is expressed in spinal astrocytes and that depletion of calcium stores from the endoplasmic reticulum by cyclopiazonic acid (CPA) resulted in a large sustained calcium entry, which was blocked by SOCC inhibitors. Using the siRNA knockdown approach, we identified STIM1 and Orai1 as primary components of SOCCs in spinal astrocytes. We also observed thapsigargin (TG)- or CPA-induced puncta formation of STIM1 and Orai1. In addition, activation of SOCCs remarkably promoted TNF-α and IL-6 production in spinal astrocytes, which were greatly attenuated by knockdown of STIM1 or Orai1. Importantly, knockdown of STIM2 and Orai1 dramatically decreased lipopolysaccharide-induced TNF-α and IL-6 production without changing cell viability.
conclusionsThis study presents the first evidence that STIM1, STIM2, and Orai1 mediate SOCE and are involved in cytokine production in spinal astrocytes. Our findings provide the basis for future assessment of SOCCs in pain and other central nervous system disorders associated with abnormal astrocyte activities.
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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.