Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy

被引:149
作者
Henshall, DC
Clark, RSB
Adelson, PD
Chen, M
Watkins, SC
Simon, RP
机构
[1] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA
[3] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA
[4] Univ Pittsburgh, Dept Physiol & Cell Biol, Pittsburgh, PA 15260 USA
关键词
D O I
10.1212/WNL.55.2.250
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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-x(L), bar, 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-x(L) 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, bar, and caspase-3 immunoreactivity was increased predominantly in cells with the morphologic appearance of neurons, whereas bcl-x(L) 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.
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页码:250 / 257
页数:8
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