The Role of CED-3-Related Cysteine Proteases in Apoptosis of Cerebellar Granule Cells

摘要: The CED-3-related cysteine proteases (CRCPs) have been implicated as mediators of apoptosis, primarily in hematogenous cell systems, but their role neuronal apoptosis remains unclear. present study examined the two CRCP families-CPP32- and interleukin-1beta converting enzyme (ICE)-like proteases-in cerebellar granule cells (CGCs) caused by withdrawal serum and/or potassium (K+). Serum deprivation potentiated K+ withdrawal, reducing viability approximately one half control values after 12 hr measured calcein fluorescence. Cell death serum/K+ was significantly attenuated CPP32-like inhibitor z-DEVD-fmk; however, ICE-like z-YVAD-fmk had only slightly protective effects at highest concentration used. Both inhibitors reduced activity directly an vitro fluorometric assay system, although z-DEVD-fmk showed much greater potency. each were accompanied increased activity; absent deprivation. CPP32 mRNA levels unchanged combined reverse transcription-PCR (RT-PCR), with peak 4 reaching 210 +/- 37% 269 42% levels, respectively. In contrast, ICE undetectable RT-PCR. These results are consistent hypothesis that play important CGCs or serum/K+.