Author Correction: Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1
| Autor: | Abraham Martín, Leonor Kremer, Christofer Ireson, Andrea Gamir-Morralla, Mª José Pérez-Álvarez, Julia Pose-Utrilla, Jesús Avila, Isidro Ferrer, Félix Hernández, Noelia S. de León-Reyes, Mónica García-Gallo, Marina Lasa, Jerónimo Jurado-Arjona, Ana del Puerto, Álvaro Sebastián-Serrano, Jens Fielitz, Miguel R. Campanero, Teresa Iglesias, Lucía García-Guerra |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Science
General Physics and Astronomy In Vitro Techniques Bioinformatics medicine.disease_cause General Biochemistry Genetics and Molecular Biology Mice Detoxification Protein Phosphatase 1 Medicine Animals Phosphorylation lcsh:Science Author Correction Protein Kinase C Mice Knockout Neurons Multidisciplinary Cell Death business.industry Superoxide Dismutase NF-kappa B Dual Specificity Phosphatase 1 General Chemistry Spelling Neuroprotection I-kappa B Kinase Oxidative Stress lcsh:Q business Oxidative stress Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-1 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders. |
| Databáze: | OpenAIRE |
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