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

• Published in: Journal of molecular neuroscience Vol. 56; no. 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: Journal Article
• Language: English
• Published: Totowa Springer Nature B.V 01.06.2015
• Subjects: Apoptosis; Cell death; Endoplasmic reticulum; MicroRNAs; Proteins; United States > US; Ireland
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0510-0

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.