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Apoptosis in Cerebellar Granule Neurones: Involvement of Interleukin‐1β Converting Enzyme‐Like Proteases
Author(s) -
Taylor Joanne,
Gatchalian Christine L.,
Keen Gregory,
Rubin Lee L.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68041598.x
Subject(s) - staurosporine , proteases , apoptosis , programmed cell death , biology , protease , microbiology and biotechnology , caspase , protein kinase a , biochemistry , inhibitor of apoptosis , enzyme , kinase
Proteases of the interleukin‐1β converting enzyme (ICE) family have been implicated as mediators of apoptosis in several cell types. Here we report the ability of peptide inhibitors of ICE‐like proteases to inhibit apoptosis of cultured cerebellar granule neurones caused by reduction of extracellular K + levels and by the broad‐spectrum protein kinase inhibitor staurosporine. Unlike apoptosis induced by K + deprivation, staurosporine‐induced neuronal death does not require new protein synthesis. The ICE‐like protease inhibitor benzyloxycarbonyl‐Val‐Ala‐Asp ( O ‐methyl)fluoromethyl ketone (zVAD‐fmk) was found to be extremely effective at preventing staurosporine‐induced death of cerebellar granule neurones and yet was completely ineffective in preventing K + deprivation‐induced death. Staurosporine induced cleavage of the 116‐kDa poly(ADP‐ribose) polymerase enzyme, a substrate of ICE‐like proteases, to the 85‐kDa product, and this cleavage was also blocked by zVAD. By comparison, K + deprivation led to the disappearance of the 116‐kDa protein, with no detectable increase in level of the 85‐kDa cleavage product. Taken together, these results imply the existence of divergent ICE‐like protease pathways in a CNS model of neuronal apoptosis.