Depletion of 14-3-3 zeta elicits endoplasmic reticulum stress and cell death, and increases vulnerability to kainate-induced injury in mouse hippocampal cultures
| Autor: | Jochen H. M. Prehn, Manus W. Ward, Niamh C. Murphy, Helena P. Bonner, Brona M. Murphy, David C. Henshall |
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| Rok vydání: | 2008 |
| Předmět: |
Programmed cell death
medicine.medical_specialty Kainic acid Calnexin Protein Sorting Signals Biology Hippocampal formation Endoplasmic Reticulum Hippocampus Biochemistry Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Organ Culture Techniques Internal medicine Excitatory Amino Acid Agonists medicine Animals RNA Small Interfering Cellular localization Neurons Analysis of Variance Veratridine Kainic Acid Cell Death Tunicamycin Endoplasmic reticulum Dentate gyrus Neurodegeneration medicine.disease Up-Regulation Cell biology Endocrinology 14-3-3 Proteins chemistry Unfolded protein response Oligopeptides Subcellular Fractions |
| Zdroj: | Journal of Neurochemistry. 106:978-988 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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