Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis

被引:110
作者
Nath, R [1 ]
Raser, KJ [1 ]
McGinnis, K [1 ]
Nadimpalli, R [1 ]
Stafford, D [1 ]
Wang, KKW [1 ]
机构
[1] PARKE DAVIS PHARMACEUT RES,LAB NEUROBIOCHEM,DEPT NEUROSCI THERAPEUT,ANN ARBOR,MI 48105
关键词
apoptosis; calpain; cerebellar granule neurons; interleukin-1 beta converting enzyme (ICE); necrosis; neuronal death; protease inhibitor; SH-SY5Y;
D O I
10.1097/00001756-199612200-00050
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
BOTH ICE-like protease and calpain have been shown to be involved in apoptosis in non-neuronal cells. Cultured rat cerebellar granule neurons undergo apoptosis when exposed to low potassium-containing medium. Calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and N-acetyl-Leu-Leu-Met-CHO (calpain inhibitor II) as well as interleukin-beta 1 converting enzyme (ICE)-like protease inhibitor Z-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB) protect against such apoptotic death. They also reduce DNA laddering and the number of apoptotic nuclei. Staurosporine treatment also evokes apoptosis in human neuroblastoma SH-SY5Y. While Z-D-DCB is again anti-apoptotic, calpain inhibitors only provide modest effects in this model. Our results suggest that ICE-like protease plays a critical role in neuronal apoptosis whereas the contributions of calpain are more cell-type dependent.
引用
收藏
页码:249 / 255
页数:7
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