Overexpression of 14-3-3[zeta] Increases Brain Levels of C/EBP Homologous Protein CHOP

Recent studies demonstrated that overexpression of the molecular chaperone 14-3-3[zeta] protects the brain against endoplasmic reticulum (ER) stress and prolonged seizures. The 14-3-3 targets responsible for improved neuronal survival after seizures remain unknown. Here we explored the mechanism, fi...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2015-06, Vol.56 (2), p.255
Main Authors: Brennan, Gary P, Jimenez-mateos, Eva M, Sanz-rodriguez, Amaya, Mooney, Claire M, Tzivion, Guri, Henshall, David C, Engel, Tobias
Format: Article
Language:English
Subjects:
Apoptosis
Cell death
Endoplasmic reticulum
MicroRNAs
Proteins
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Summary:Recent studies demonstrated that overexpression of the molecular chaperone 14-3-3[zeta] protects the brain against endoplasmic reticulum (ER) stress and prolonged seizures. The 14-3-3 targets responsible for improved neuronal survival after seizures remain unknown. Here we explored the mechanism, finding that protein levels of the ER-stress-associated transcription factor C/EBP homologous protein (CHOP) were significantly higher in 14-3-3[zeta]-overexpressing mice. Since previous studies by us demonstrated that loss of CHOP increased vulnerability to seizure damage, we explored whether elevated CHOP levels result from 14-3-3[zeta] overexpression and contribute to the protection. Pull-down experiments suggested that 14-3-3[zeta] could bind CHOP as well as sequester a CHOP-targeting microRNA. However, 14-3-3[zeta] overexpression remained protective against seizure-induced hippocampal injury in mice lacking CHOP. These studies reveal a novel function for 14-3-3[zeta] in regulating CHOP levels but show that this is not required for protection against seizure-induced neuronal death.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-015-0510-0