Proteomic identification of the involvement of the mitochondrial rieske protein in epilepsy.
OBJECTIVE
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.
Junker
Heike
H
Institutes of Biochemistry, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Späte
Kira
K
Suofu
Yalikun
Y
Walther
Reinhard
R
Schwarz
Gerold
G
Kammer
Winfried
W
Nordheim
Alfred
A
Walker
Lary C
LC
Runge
Uwe
U
Kessler
Christof
C
Popa-Wagner
Aurel
A
D000818:Animals; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D014450:Electron Transport Complex III / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007506:Iron-Sulfur Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000235:genetics*; D008297:Male; D013058:Mass Spectrometry; D024101:Mitochondrial Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010433:Pentylenetetrazole; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; C037989:Rieske iron-sulfur protein; D014450:Electron Transport Complex III; D010433:Pentylenetetrazole