ArticleThe Journal of biological chemistry2014
Ischemia-like oxygen and glucose deprivation mediates down-regulation of cell surface γ-aminobutyric acidB receptors via the endoplasmic reticulum (ER) stress-induced transcription factor CCAAT/enhancer-binding protein (C/EBP)-homologous protein (CHOP).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAScientific reports · 2025Article
- Optimization of neuron-specific interfering peptides targeting GABAFrontiers in pharmacology · 2025Article
- Endoplasmic reticular stress as an emerging therapeutic target for chronic pain: a narrative review.British journal of anaesthesia · 2024Review
- Restoration of GABANeural regeneration research · 2023Article
- Research Progress on the Mechanisms of Central Post-Stroke Pain: A Review.Cellular and molecular neurobiology · 2023Review
- Targeting the interaction of GABABrain pathology (Zurich, Switzerland) · 2023Article
- Investigating a Genetic Link Between Alzheimer's Disease and CADASIL-Related Cerebral Small Vessel Disease.Molecular neurobiology · 2022Article
- Protein phosphatase 2A regulation of GABAFrontiers in molecular neuroscience · 2022Article
- Targeting the Interaction of GABAFrontiers in pharmacology · 2022Article
- EETs/sEHi alleviates nociception by blocking the crosslink between endoplasmic reticulum stress and neuroinflammation in a central poststroke pain model.Journal of neuroinflammation · 2021Article
- Age and sex modify cellular proliferation responses to oxidative stress and glucocorticoid challenges in baboon cells.GeroScience · 2021Article
- Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis.Molecular medicine reports · 2021Article
- Sustained Baclofen-Induced Activation of GABAFrontiers in molecular neuroscience · 2021Article
- Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.Mediators of inflammation · 2021Review
- Liver-specific knockout of histone methyltransferase G9a impairs liver maturation and dysregulates inflammatory, cytoprotective, and drug-processing genes.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- CaMolecular neurobiology · 2019Article
- Dexmedetomidine Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetes Mellitus by Inhibiting Endoplasmic Reticulum Stress.Journal of diabetes research · 2019Article
- The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs.Oxidative medicine and cellular longevity · 2019Review
- UBIAD1 protects against oxygen-glucose deprivation/reperfusion-induced multiple subcellular organelles injury through PI3K/AKT pathway in N2A cells.Journal of cellular physiology · 2018Article
- GABABMC cancer · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral ischemia frequently leads to long-term disability and death. Excitotoxicity is believed to be the main cause for ischemia-induced neuronal death. Although a role of glutamate receptors in this process has been firmly established, the contribution of metabotropic GABAB receptors, which control excitatory neurotransmission, is less clear. A prominent characteristic of ischemic insults is endoplasmic reticulum (ER) stress associated with the up-regulation of the transcription factor CCAAT/enhancer-binding protein-homologous protein (CHOP). After inducing ER stress in cultured cortical neurons by sustained Ca(2+) release from intracellular stores or by a brief episode of oxygen and glucose deprivation (in vitro model of cerebral ischemia), we observed an increased expression of CHOP accompanied by a strong reduction of cell surface GABAB receptors. Our results indicate that down-regulation of cell surface GABAB receptors is caused by the interaction of the receptors with CHOP in the ER. Binding of CHOP prevented heterodimerization of the receptor subunits GABAB1 and GABAB2 and subsequent forward trafficking of the receptors to the cell surface. The reduced level of cell surface receptors diminished GABAB receptor signaling and, thus, neuronal inhibition. These findings indicate that ischemia-mediated up-regulation of CHOP down-regulates cell surface GABAB receptors by preventing their trafficking from the ER to the plasma membrane. This mechanism leads to diminished neuronal inhibition and may contribute to excitotoxicity in cerebral ischemia.
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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.