ArticleThe Journal of biological chemistry2008
Morphine induces ubiquitin-proteasome activity and glutamate transporter degradation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- PTEN: a new dawn in Parkinson's disease treatment.Frontiers in cellular neuroscience · 2025Review
- The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.Frontiers in pharmacology · 2024Article
- The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats.Frontiers in pharmacology · 2024Article
- The ubiquitin-proteasome system and learning-dependent synaptic plasticity - A 10 year update.Neuroscience and biobehavioral reviews · 2023Review
- Lipophilic analogues of D-cysteine prevent and reverse physical dependence to fentanyl in male rats.Frontiers in pharmacology · 2023Article
- L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats.Frontiers in pharmacology · 2023Article
- Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.Molecules (Basel, Switzerland) · 2022Article
- Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants (Basel, Switzerland) · 2022Review
- Dysregulation of Vesicular Glutamate Transporter VGluT2Frontiers in pharmacology · 2022Article
- Role of the Ubiquitin System in Chronic Pain.Frontiers in molecular neuroscience · 2021Review
- Identification of Anti-Frontiers in microbiology · 2020Article
- Interplay between the Endogenous Opioid System and Proteasome Complex: Beyond Signaling.International journal of molecular sciences · 2019Review
- SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway.Technology in cancer research & treatment · 2018Article
- Neurobiological Effects of Morphine after Spinal Cord Injury.Journal of neurotrauma · 2017Article
- Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt.Acta pharmacologica Sinica · 2017Article
- Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury.Spinal cord · 2016Article
- The importance of the excitatory amino acid transporter 3 (EAAT3).Neurochemistry international · 2016Review
- Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway.Scientific reports · 2016Article
- Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Glutamate transporters play a crucial role in physiological glutamate homeostasis, neurotoxicity, and glutamatergic regulation of opioid tolerance. However, how the glutamate transporter turnover is regulated remains poorly understood. Here we show that chronic morphine exposure induced posttranscriptional down-regulation of the glutamate transporter EAAC1 in C6 glioma cells with a concurrent decrease in glutamate uptake and increase in proteasome activity, which were blocked by the selective proteasome inhibitor MG-132 or lactacystin but not the lysosomal inhibitor chloroquin. At the cellular level, chronic morphine induced the PTEN (phosphatase and tensin homolog deleted on chromosome Ten)-mediated up-regulation of the ubiquitin E3 ligase Nedd4 via cAMP/protein kinase A signaling, leading to EAAC1 ubiquitination and proteasomal degradation. Either Nedd4 or PTEN knockdown with small interfering RNA prevented the morphine-induced EAAC1 degradation and decreased glutamate uptake. These data indicate that cAMP/protein kinase A signaling serves as an intracellular regulator upstream to the activation of the PTEN/Nedd4-mediated ubiquitin-proteasome system activity that is critical for glutamate transporter turnover. Under an in vivo condition, chronic morphine exposure also induced posttranscriptional down-regulation of the glutamate transporter EAAC1, which was prevented by MG-132, and transcriptional up-regulation of PTEN and Nedd4 within the spinal cord dorsal horn. Thus, inhibition of the ubiquitin-proteasome-mediated glutamate transporter degradation may be an important mechanism for preventing glutamate overexcitation and may offer a new strategy for treating certain neurological disorders and improving opioid therapy in chronic pain management.
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Registered trials
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.