Isoform- and Subcellular Fraction-specific Differences in Hippocampal 14-3-3 Levels Following Experimentally Evoked Seizures and in Human Temporal Lobe Epilepsy.
From: Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA.
Journal of neurochemistry
- Publish Date: Oct 2006
- ISSN: 0022-3042
- Volume: 99
- Issue: 2
- Pages: 561-9
- Medium: Print
- Language: English
- Citation (JAMA): Schindler Clara K, Heverin Maura, Henshall David C, et al. Isoform- and Subcellular Fraction-specific Differences in Hippocampal 14-3-3 Levels Following Experimentally Evoked Seizures and in Human Temporal Lobe Epilepsy.. J. Neurochem. Oct 2006;99:561-9
Abstract
14-3-3 proteins are a family of signaling molecules involved in diverse cellular functions, which can mediate anti-apoptotic effects. Seizure-induced neuronal death may involve programmed (apoptotic) cell death pathways and is associated with a decline in brain 14-3-3 levels. Presently, we investigated the subcellular localization and effects of seizures on isoforms of 14-3-3 in rat hippocampus, and contrasted these to findings in human temporal lobe epilepsy (TLE). All brain isoforms of 14-3-3 were detected in the cytoplasmic compartment of rat hippocampus, while 14-3-3gamma and -zeta were also present in mitochondrial and microsome-enriched fractions. Focally evoked seizures in rats significantly reduced 14-3-3gamma levels within the microsome-enriched compartment at 4 h, with similar responses for 14-3-3zeta, while cytoplasm-localized 14-3-3beta, -epsilon and -eta remained unchanged. Analysis of human autopsy control hippocampus revealed similar 14-3-3 isoform expression profiles. In TLE samples, the microsome-enriched fraction also showed differences, but here 14-3-3epsilon and -zeta levels were higher than controls. TLE sample 14-3-3 isoform abundance within the cytoplasmic fraction was not different to controls. This study defines the subcellular localization of 14-3-3 isoforms in rat and human hippocampus and identifies the microsome-enriched fraction as the main site of altered 14-3-3 levels in response to acute prolonged and chronic recurrent seizures.
Mesh Headings (Keywords): 14-3-3 Proteins, Adolescent, Adult, Animals, Apoptosis, Cell Compartmentation, Cytoplasm, Disease Models, Animal, Epilepsy, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Male, Microsomes, Middle Aged, Mitochondria, Nerve Degeneration, Protein Isoforms, Rats, Subcellular Fractions
Check for Full Text / PubMed Unique Identifier (PMID): 16981892
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