Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy.
OBJECTIVE
To address the role of cell death regulatory genes of the bcl-2 and caspase families in the neuropathology of human epilepsy using tissue extracted from patients undergoing temporal lobectomy for intractable seizures.


METHODS
Using Western blotting and immunohistochemistry, the authors investigated the expression of bcl-2, bcl-xL, bax, caspase-1,and caspase-3 in temporal cortex samples from patients who had undergone temporal lobectomy surgery for intractable epilepsy (n = 19). Nonepileptic postmortem tissue from a brain bank served as control (n = 6).


RESULTS
Western blot analysis demonstrated significant increases in levels of bcl-2 and bcl-xL protein in seizure brain compared to control. Cleavage of caspase-1 was evidenced by a reduction in levels of the 45 kDa proenzyme form and an increase in levels of the p10 fragment. Levels of the 32 kDa proenzyme form of caspase-3 were elevated in seizure patients, as were levels of the 12 kDa cleaved fragment. Bcl-2, bax, and caspase-3 immunoreactivity was increased predominantly in cells with the morphologic appearance of neurons, whereas bcl-xL immunoreactivity was increased in cells with the appearance of glia. DNA fragmentation was detected in some but not all sections from epileptic brain samples.


CONCLUSIONS
Cell death regulatory genes of the bcl-2 and caspase families may play a role in ongoing neuropathologic processes in human epilepsy, and offer novel targets as an adjunct to anticonvulsant therapy.
Henshall
D C
DC
Department of Neurology, University of Pittsburgh, PA, USA.
Clark
R S
RS
Adelson
P D
PD
Chen
M
M
Watkins
S C
SC
Simon
R P
RP
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D020170:Caspase 1 / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013702:Temporal Lobe / Q000473:pathology
D019253:Proto-Oncogene Proteins c-bcl-2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1