Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3 levels following experimentally evoked seizures and in human temporal lobe epilepsy
Article first published online: 8 AUG 2006
Journal of Neurochemistry
Volume 99, Issue 2, pages 561–569, October 2006
How to Cite
Schindler, C. K., Heverin, M. and Henshall, D. C. (2006), Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3 levels following experimentally evoked seizures and in human temporal lobe epilepsy. Journal of Neurochemistry, 99: 561–569. doi: 10.1111/j.1471-4159.2006.04153.x
- Issue published online: 8 AUG 2006
- Article first published online: 8 AUG 2006
- Received May 26, 2006; revised manuscript received June 13, 2006; accepted June 13, 2006.
- endoplasmic reticulum;
- programmed cell death
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 14-3-3γ and -ζ were also present in mitochondrial and microsome-enriched fractions. Focally evoked seizures in rats significantly reduced 14-3-3γ levels within the microsome-enriched compartment at 4 h, with similar responses for 14-3-3ζ, while cytoplasm-localized 14-3-3β, -ε and -η 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 14-3-3ε and -ζ 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.