ArticleThe Journal of biological chemistry2011
Dual-specific phosphatase-6 (Dusp6) and ERK mediate AMPA receptor-induced oligodendrocyte death.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
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- Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?Annual review of pharmacology and toxicology · 2023Review
- Exploring the therapeutic potential of the mitochondrial transfer-associated enzymatic machinery in brain degeneration.Frontiers in physiology · 2023Review
- Effect of β-hydroxybutyrate on behavioral alterations, molecular and morphological changes in CNS of multiple sclerosis mouse model.Frontiers in aging neuroscience · 2022Article
- Oligodendrocytes, BK channels and the preservation of myelin.F1000Research · 2021Review
- Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage.Frontiers in cell and developmental biology · 2020Article
- Glutamate Carrier Involvement in Mitochondrial Dysfunctioning in the Brain White Matter.Frontiers in molecular biosciences · 2020Article
- Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells.International journal of molecular sciences · 2019Review
- Catalpol Inhibits Ischemia-Induced Premyelinating Oligodendrocyte Damage through Regulation of Intercellular Calcium Homeostasis via Na⁺/CaInternational journal of molecular sciences · 2018Article
- Aloe-emodin as drug candidate for cancer therapy.Oncotarget · 2018Article
- The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target (Review).International journal of molecular medicine · 2017Review
- Signalling mechanisms mediating ZnScientific reports · 2017Article
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- Effects of Abies sibirica terpenes on cancer- and aging-associated pathways in human cells.Oncotarget · 2016Article
- MAP kinase phosphatase 2 deficient mice develop attenuated experimental autoimmune encephalomyelitis through regulating dendritic cells and T cells.Scientific reports · 2016Article
- Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction.Journal of molecular medicine (Berlin, Germany) · 2015Article
- Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus.PloS one · 2013Article
- Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells.Bioscience reports · 2012Article
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Authors and funding
6 authors.
Funding
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Abstract
Oligodendrocytes, the myelinating cells of the CNS, are highly vulnerable to glutamate excitotoxicity, a mechanism involved in tissue damage in multiple sclerosis. Thus, understanding oligodendrocyte death at the molecular level is important to develop new therapeutic approaches to treat the disease. Here, using microarray analysis and quantitative PCR, we observed that dual-specific phosphatase-6 (Dusp6), an extracellular regulated kinase-specific phosphatase, is up-regulated in oligodendrocyte cultures as well as in optic nerves after AMPA receptor activation. In turn, Dusp6 is overexpressed in optic nerves from multiple sclerosis patients before the appearance of evident damage in this structure. We further analyzed the role of Dusp6 and ERK signaling in excitotoxic oligodendrocyte death and observed that AMPA receptor activation induces a rapid increase in ERK1/2 phosphorylation. Blocking Dusp6 expression, which enhances ERK1/2 phosphorylation, significantly diminished AMPA receptor-induced oligodendrocyte death. In contrast, MAPK/ERK pathway inhibition with UO126 significantly potentiates excitotoxic oligodendrocyte death and increases cytochrome c release, mitochondrial depolarization, and mitochondrial calcium overload produced by AMPA receptor stimulation. Upstream analysis demonstrated that MAPK/ERK signaling alters AMPA receptor properties. Indeed, Dusp6 overexpression as well as incubation with UO126 produced an increase in AMPA receptor-induced inward currents and cytosolic calcium overload. Together, these data suggest that levels of phosphorylated ERK, controlled by Dusp6 phosphatase, regulate glutamate receptor permeability and oligodendroglial excitotoxicity. Therefore, targeting Dusp6 may be a useful strategy to prevent oligodendrocyte death in multiple sclerosis and other diseases involving CNS white matter.
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