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Proteomic Identification of the Involvement of the Mitochondrial Rieske Protein in Epilepsy
Author(s) -
Junker Heike,
Späte Kira,
Suofu Yalikun,
Walther Reinhard,
Schwarz Gerold,
Kammer Winfried,
Nordheim Alfred,
Walker Lary C.,
Runge Uwe,
Kessler Christof,
PopaWagner Aurel
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.0013-9580.2005.46904.x
Subject(s) - epileptogenesis , kindling , dentate gyrus , epilepsy , neuroscience , kindling model , neurogenesis , hippocampus , biology , subgranular zone , status epilepticus , microbiology and biotechnology , neural stem cell , stem cell , subventricular zone
Summary: Purpose: Kindled seizures are widely used to model epileptogenesis, but the molecular mechanisms underlying the attainment of kindling status are largely unknown. Recently we showed that achievement of kindling status in the Sprague–Dawley rat is associated with a critical developmental interval of 25 ± 1 days; the identification of this long, well‐defined developmental interval for inducing kindling status makes possible a dissection of the cellular and genetic events underlying this phenomenon and its relation to normal and pathologic brain function. Methods: By using proteomics on cerebral tissue from our new rat kindling model, we undertook a global analysis of protein expression in kindled animals. Some of the identified proteins were further investigated by using immunohistochemistry. Results: We report the identification of a modified variant of the Rieske iron‐sulfur protein, a component of the mitochondrial cytochrome bc1 complex, whose isoelectric point is shifted toward more alkaline values in the hippocampus of kindled rats. By immunohistochemistry, the Rieske protein is well expressed in the hippocampus, except in the CA1 subfield, an area of selective vulnerability to seizures in humans and animal models. We also noted an asymmetric, selective expression of the Rieske protein in the subgranular neurons of the dorsal dentate gyrus, a region implicated in neurogenesis. Conclusions: These results indicate that the Rieske protein may play a role in the response of neurons to seizure activity and could give important new insights into the molecular pathogenesis of epilepsy.