Caspase 6 activity initiates caspase 3 activation in cerebellar granule cell apoptosis

被引：115

作者：

Allsopp, TE ^{[1
]}

McLuckie, J ^{[1
]}

Kerr, LE ^{[1
]}

Macleod, M ^{[1
]}

Sharkey, J ^{[1
]}

Kelly, JS ^{[1
]}

机构：

[1] Univ Edinburgh, Dept Neurosci, FINE, Edinburgh EH8 9JZ, Midlothian, Scotland

来源：

CELL DEATH AND DIFFERENTIATION | 2000年 / 7卷 / 10期

关键词：

apoptosis; caspase; 3; 6; cerebellar granule cells; zVADfmk; trophic support withdrawal;

D O I：

10.1038/sj.cdd.4400733

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Using a well documented ex vivo system consisting of rodent cerebellar granule cells (CGCs) the activation of caspases 3 and 6 during apoptosis induced by withdrawal of trophic support was analyzed, At the time of deprivation, the addition of the irreversible, broad-spectrum caspase inhibitor zVADfmk or the cell permeable, caspase 6 inhibitor CP-VEID-cho can transiently suppress the appearance of apoptosis, including the early appearance of DNA fragmentation. Using immunoblotting and fluorogenic peptide assays we observe deprivation-induced activation of caspases 3 and 6, but not caspase 9, Furthermore, active caspase 6 is capable of processing and activating procaspase 3 in cellular extracts prepared from non-apoptotic CGCs, whereas caspase 3 failed to activate caspase 6, In consonant with this, the cell permeable caspase 6 inhibitor prevented deprivation induced caspase 3 activation whereas a cell permeable caspase 3 inhibitor, CP-DEVD-cho, had no effect on caspase 6 activation. This would indicate that caspase 6 is a significant inducer of the early caspase 3 activity in apoptotic CGCs.

引用

页码：984 / 993

页数：10

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