Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3 levels following experimentally evoked seizures and in human temporal lobe epilepsy.
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.
Schindler
Clara K
CK
Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA.
Heverin
Maura
M
Henshall
David C
DC
D048948:14-3-3 Proteins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D048948:14-3-3 Proteins; D020033:Protein Isoforms