ArticleMolecular pharmacology2008
Selective inhibition of mitogen-activated protein kinase phosphatases by zinc accounts for extracellular signal-regulated kinase 1/2-dependent oxidative neuronal cell death.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed, 98 citations in OpenAlex.
- Ion-Driven Regulation of CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Zinc suppresses Stat3-driven IL-6 production in primary mouse adipocytes.Frontiers in immunology · 2026Article
- The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways.BMC pulmonary medicine · 2022Article
- Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury.International journal of molecular sciences · 2021Article
- Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension.Cell communication and signaling : CCS · 2021Article
- ZnProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse.Frontiers in immunology · 2021Article
- Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.Cellular and molecular life sciences : CMLS · 2020Review
- Activated Erk Is an Early Retrograde Signal After Spinal Cord Injury in the Lamprey.Frontiers in neuroscience · 2020Article
- DR region of NaScientific reports · 2018Article
- Zinc Potentiates Lipopolysaccharide-induced Nitric Oxide Production in Cultured Primary Rat Astrocytes.Neurochemical research · 2018Article
- Zinc as a Gatekeeper of Immune Function.Nutrients · 2017Review
- Zinc Signals and Immunity.International journal of molecular sciences · 2017Review
- α-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress.International journal of molecular sciences · 2017Article
- Article
- Zn(2+) at a cellular crossroads.Current opinion in chemical biology · 2016Review
- The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor.Frontiers in neuroscience · 2016Article
- Review
- Zinc and the aging brain.Genes & nutrition · 2014Article
- Mitogen-activated protein kinase phosphatase-1 inhibition and sustained extracellular signal-regulated kinase 1/2 activation in camptothecin-induced human colon cancer cell death.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress induced by glutathione depletion in the mouse HT22 neuroblastoma cell line and embryonic rat immature cortical neurons causes a delayed, sustained activation of extracellular signal-regulated kinase (ERK) 1/2, which is required for cell death. This sustained activation of ERK1/2 is mediated primarily by a selective inhibition of distinct ERK1/2-directed phosphatases either by enhanced degradation (i.e., for mitogen-activated protein kinase phosphatase-1) or as shown here by reductions in enzymatic activity (i.e., for protein phosphatase type 2A). The inhibition of ERK1/2 phosphatases in HT22 cells and immature neurons subjected to glutathione depletion results from oxidative stress because phosphatase activity is restored in cells treated with the antioxidant butylated hydroxyanisole. This leads to reduced ERK1/2 activation and neuroprotection. Furthermore, an increase in free intracellular zinc that accompanies glutathione-induced oxidative stress in HT22 cells and immature neurons contributes to selective inhibition of ERK1/2 phosphatase activity and cell death. Finally, ERK1/2 also functions to maintain elevated levels of zinc. Thus, the elevation of intracellular zinc within neurons subjected to oxidative stress can trigger a robust positive feedback loop operating through activated ERK1/2 that rapidly sets into motion a zinc-dependent pathway of cell death.
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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.