Shifted cytosolic NADP(+)-dependent isocitrate dehydrogenase on 2-D gel inthe brain of genetically epileptic El mice

We observed a spot on two-dimensional (2-D) gel in the epileptic mutant str ain El mice with a similar molecular weight but with a different isoelectri c point of approximately 0.2, compared with its mother strain ddY mice. The collected protein from the El mice was identified as cytosolic NADP(+)-dep endent isocitrate dehydrogenase by internal amino acid sequencing. The enzy me is known to be maximally active during the development of the brain and to play an important role in NADPH production for fatty acids and cholester ol synthesis. In addition, alterations in cholesterol synthesis early in th e development of the mammalian brain have been reported to lead to chronic epilepsy. The results in the present study therefore suggest that cytosolic NADP(+)-dependent isocitrate dehydrogenase might be involved in the epilep togenesis of the El mouse.