Type

Journal Article

Authors

David C Henshall
Jochen H M Prehn
Brona M Murphy
Manus W Ward
Helena P Bonner
Niamh Murphy

Subjects

Biochemistry

Topics
cell death lysyl aspartyl glutamyl leucine subcellular fractions veratridine pharmacology kainic acid excitatory amino acid agonists animals protein sorting signals mice tunicamycin calnexin ultrastructure metabolism analysis of variance hippocampus cytology drug effects endoplasmic reticulum 14 3 3 proteins organ culture techniques toxicity rna small interfering oligopeptides neurons up regulation

Depletion of 14-3-3 zeta elicits endoplasmic reticulum stress and cell death, and increases vulnerability to kainate-induced injury in mouse hippocampal cultures. (2008)

Abstract 14-3-3 proteins are ubiquitous signalling molecules that regulate development and survival pathways in brain. Altered expression and cellular localization of 14-3-3 proteins has been implicated in neurodegenerative diseases and in neuronal death after acute neurological insults, including seizures. Presently, we examined expression and function of 14-3-3 isoforms in vitro using mouse organotypic hippocampal cultures. Treatment of cultures with the endoplasmic reticulum (ER) stressor tunicamycin caused an increase in levels of 14-3-3 zeta within the ER-containing microsomal fraction, along with up-regulation of Lys-Asp-Glu-Leu-containing proteins and calnexin, and the selective death of dentate granule cells. Depletion of 14-3-3 zeta levels using small interfering RNA induced both ER stress proteins and death of granule cells. Treatment of hippocampal cultures with the excitotoxin kainic acid increased levels of Lys-Asp-Glu-Leu-containing proteins and microsomal 14-3-3 zeta levels and caused cell death within the CA1, CA3 and dentate gyrus of the hippocampus. Kainic acid-induced damage was significantly increased in each hippocampal subfield of cultures treated with small interfering RNA targeting 14-3-3 zeta. The present data indicate a role for 14-3-3 zeta in survival responses following ER stress and possibly protection against seizure injury to the hippocampus.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Jochen H M Prehn, Brona M Murphy, Manus W Ward, Helena P Bonner, Niamh Murphy

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
3
Brona M Murphy
Royal College of Surgeons in Ireland
Total Publications: 14
 
4
Helena P Bonner
Royal College of Surgeons in Ireland
Total Publications: 15