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Role of Calpain‐ and Interleukin‐1β Converting Enzyme‐Like Proteases in the β‐Amyloid‐Induced Death of Rat Hippocampal Neurons in Culture
Author(s) -
Jordán Joaquín,
Galindo María F.,
Miller Richard J.
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.1471-4159.1997.68041612.x
Subject(s) - calpain , staurosporine , proteases , spectrin , programmed cell death , biology , leupeptin , microbiology and biotechnology , hippocampal formation , apoptosis , protease , biochemistry , cysteine protease , protein kinase c , enzyme , endocrinology , cytoskeleton , cell
We investigated the potential role of different proteases in the death of cultured rat hippocampal pyramidal neurons induced by β‐amyloid(Aβ) (25–35). Both Aβ(25–35)‐ and staurosporine‐induced death of these neurons appeared to involve apoptosis, as indicated using Hoechst 33342 and terminal dUDP nick end labeling staining, whereas NMDA‐induced death appeared more complex. Two irreversible inhibitors of the interleukin‐1β converting enzyme (ICE) and related proteases, Z‐Val‐Ala‐Asp‐CH 2 F and acetyl‐Tyr‐Val‐Ala‐Asp‐chloromethyl ketone, blocked neuronal death produced by Aβ(25–35), staurosporine, and NMDA to differing extents. Furthermore, MDL 28,170, a selective inhibitor of the calcium‐regulated protease calpain, also inhibited death induced by all agents. Aβ(25–35) and staurosporine stimulated the breakdown of the protein spectrin, a calpain substrate. Spectrin breakdown was inhibited by MDL 28,170 but not by ICE inhibitors. Leupeptin was only effective in preventing NMDA‐induced death. These results support the role of apoptosis in neuronal death due to Aβ(25–35) treatment and also suggest a role for calcium‐regulated proteases in this process.