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231225s2021 xx |||||o 00| ||eng c |
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|a 10.1155/2021/4090441
|2 doi
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|a pubmed24n1100.xml
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|a DE-627
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| 041 |
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|a eng
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| 100 |
1 |
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|a Xu, Linhao
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a Suppression of CHOP Reduces Neuronal Apoptosis and Rescues Cognitive Impairment Induced by Intermittent Hypoxia by Inhibiting Bax and Bak Activation
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| 264 |
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1 |
|c 2021
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| 336 |
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|a Text
|b txt
|2 rdacontent
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| 337 |
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 04.02.2022
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| 500 |
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|a Date Revised 04.02.2022
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|a published: Electronic-eCollection
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|a Citation Status MEDLINE
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| 520 |
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|a Copyright © 2021 Linhao Xu et al.
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|a Our previous study showed that growth arrest- and DNA damage-inducible gene 153 (GAD153/CHOP) plays an important role in intermittent hypoxia- (IH-) induced apoptosis and impaired synaptic plasticity. This study is aimed at determining which signaling pathway is activated to induce CHOP and the role of this protein in mitochondria-dependent apoptosis induced by IH. In the in vivo study, mice were placed in IH chambers for 8 h daily over a period of 2 weeks; the IH chambers had oxygen (O2) concentrations that oscillated between 10% and 21%, cycling every 90 s. In the in vitro study, PC12 cells were exposed to 21% O2 (normoxia) or 8 IH cycles (25 min at 21% O2 and 35 min at 0.1% O2 for each cycle). After 2 weeks of IH treatment, we observed that the expression levels of phosphorylated protein kinase-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF-4) and phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α), were increased, but the levels of activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1) were not increased. GSK2606414, a specific chemical inhibitor of the PERK pathway, reduced the expression of p-PERK, ATF-4, p-elf2α, and CHOP and rescued ER structure. In addition, Bax and Bak accumulated in the mitochondria after IH treatment, which induced cytochrome c release and initiated apoptosis. These effects were prevented by GSK2606414 and CHOP shRNA. Finally, the impaired long-term potentiation and long-term spatial memory in the IH group were rescued by GSK2606414. Together, the data from the in vitro and in vivo experiments indicate that IH-induced apoptosis and impaired synaptic plasticity were mediated by the PERK-ATF-4-CHOP pathway. Suppressing PERK-ATF-4-CHOP signaling pathway attenuated mitochondria-dependent apoptosis by reducing the expression of Bax and Bak in mitochondria, which may serve as novel adjunct therapeutic strategy for ameliorating obstructive sleep apnea- (OSA-) induced neurocognitive impairment
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a 7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine
|2 NLM
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| 650 |
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|a Bak1 protein, mouse
|2 NLM
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| 650 |
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|a Bax protein, mouse
|2 NLM
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| 650 |
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|a Ddit3 protein, mouse
|2 NLM
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| 650 |
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|a Indoles
|2 NLM
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| 650 |
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|a bcl-2 Homologous Antagonist-Killer Protein
|2 NLM
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| 650 |
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|a bcl-2-Associated X Protein
|2 NLM
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| 650 |
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|a Transcription Factor CHOP
|2 NLM
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| 650 |
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7 |
|a 147336-12-7
|2 NLM
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| 650 |
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7 |
|a Adenine
|2 NLM
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| 650 |
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7 |
|a JAC85A2161
|2 NLM
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| 700 |
1 |
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|a Bi, Yanli
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Xu, Yizhou
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wu, Yihao
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Du, Xiaoxue
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mou, Yixuan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chen, Jian
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Neural plasticity
|d 1998
|g 2021(2021) vom: 25., Seite 4090441
|w (DE-627)NLM098558390
|x 1687-5443
|7 nnns
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| 773 |
1 |
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|g volume:2021
|g year:2021
|g day:25
|g pages:4090441
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|u http://dx.doi.org/10.1155/2021/4090441
|3 Volltext
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