Regulation of hypoxic neuronal death signaling by neuroglobin
Autor: | Gary M. Bokoch, Céline DerMardirossian, Kunlin Jin, David A. Greenberg, Adil A. Khan, Surita Banwait, Xiao Ou Mao |
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Rok vydání: | 2008 |
Předmět: |
Neuroglobin
Mice Transgenic Nerve Tissue Proteins Biology medicine.disease_cause Biochemistry Neuroprotection Article Mice Membrane Microdomains Genetics medicine Animals Globin Hypoxia Molecular Biology Cerebral Cortex Neurons Lipid microdomain Cholera toxin Hypoxia (medical) Actins Globins Cell biology p21-Activated Kinases Death-inducing signaling complex Signal transduction medicine.symptom Signal Transduction Biotechnology |
Zdroj: | The FASEB Journal. 22:1737-1747 |
ISSN: | 1530-6860 0892-6638 |
DOI: | 10.1096/fj.07-100784 |
Popis: | The signal transduction pathways involved in neuronal death are not well understood. Neuroglobin (Ngb), a recently discovered vertebrate globin expressed predominantly in the brain, shows increased expression in neurons in response to oxygen deprivation and protects neurons from ischemic and hypoxic death. The mechanism of this neuroprotection is unclear. We examined the surface distribution of raft membrane microdomains in cortical neuron cultures during hypoxia using the raft marker cholera toxin B (CTx-B) subunit Mechanistically, we demonstrate that hypoxia induces rapid polarization of somal membranes and aggregation of microdomains with the subjacent mitochondrial network. This signaling complex is formed well before neurons commit to die, consistent with an early role in death signal transduction. Ngb-expressing neurons and neurons from Ngb-overexpressing transgenic (Ngb-Tg) mice do not undergo microdomain polarization or mitochondrial aggregation in response to, and are resistant to death from hypoxia. We link the protective actions of Ngb to inhibition of Pak1 kinase activity and Rac1-GDI disassociation, and inhibition of actin assembly and death-signaling module polarization. |
Databáze: | OpenAIRE |
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