Shifted cytosolic NADP+-dependent isocitrate dehydrogenase on 2-D gel in the brain of genetically epileptic E1 mice.

We observed a spot on two-dimensional (2-D) gel in the epileptic mutant strain E1 mice with a similar molecular weight but with a different isoelectric point of approximately 0.2, compared with its mother strain ddY mice. The collected protein from the E1 mice was identified as cytosolic NADP+-dependent isocitrate dehydrogenase by internal amino acid sequencing. The enzyme 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 cholesterol synthesis. In addition, alterations in cholesterol synthesis early in the 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 epileptogenesis of the E1 mouse.