Modified variant of the Rieske iron-sulfur protein in the hippocampus of kindled rats and human epileptic patients.
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 relationship to normal and pathological brain function. Now we report the identification, by proteomics, 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, a region 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. Abnormal changes in Rieske protein immunoreactivity also were found in sections obtained from human epileptic patients. These results suggest 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.
Petcu
E B
EB
Department of Neurology, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Dunoiu
Carmen
C
Ioana
M
M
Pirici
D
D
Mogoantă
L
L
Popa-Wagner
A
A
D000818:Animals; D014450:Electron Transport Complex III / Q000378:metabolism*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000378:metabolism / Q000473:pathology; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010433:Pentylenetetrazole; D020033:Protein Isoforms / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; C037989:Rieske iron-sulfur protein; D014450:Electron Transport Complex III; D010433:Pentylenetetrazole