Abstract
Brain ischemia causes neuronal injury leading to stroke and other related brain diseases. However, the precise mechanism of the ischemia-induced neuronal death remains unclear yet. In this study, we showed that CIIA suppressed neuronal cell death induced by oxygen and glucose deprivation followed by reoxygenation (OGD/R), which mimics ischemia and reperfusion in vivo, in neuroblastoma cell lines as well as primary cortical neurons. Furthermore, CIIA inhibited the OGD/R-induced stimulation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream kinases including c-Jun amino-terminal kinase and p38 kinase, concomitantly blocking ASK1 homo-oligomerization and the binding between ASK1 and TRAF2. CIIA also repressed the OGD/R-induced activation of caspase-3 in neuronal cells. Taken together, our results suggest that CIIA attenuates neurotoxicity caused by OGD/R through inhibiting ASK1-dependent signaling events.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cell Death / genetics
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Cell Hypoxia / genetics
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Cell Line, Tumor
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Glucose / genetics
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Glucose / metabolism*
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Humans
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MAP Kinase Kinase Kinase 5 / genetics
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MAP Kinase Kinase Kinase 5 / metabolism
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Mice
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Neurons / metabolism*
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Neurons / pathology
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Oxygen / metabolism*
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Signal Transduction*
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TNF Receptor-Associated Factor 2 / genetics
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TNF Receptor-Associated Factor 2 / metabolism
Substances
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CIIA protein, mouse
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Carrier Proteins
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Endosomal Sorting Complexes Required for Transport
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TNF Receptor-Associated Factor 2
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VPS28 protein, human
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MAP Kinase Kinase Kinase 5
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MAP3K5 protein, human
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Map3k5 protein, mouse
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CASP3 protein, human
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Casp3 protein, mouse
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Caspase 3
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Glucose
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Oxygen