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Glutamate Neurotoxicity Is Independent of Calpain I Inhibition in Primary Cultures of Cerebellar Granule Cells
Author(s) -
Manev Hari,
Favaron Marco,
Siman Robert,
Guidotti Alessandro,
Costa Erminio
Publication year - 1991
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 - 10.1111/j.1471-4159.1991.tb08292.x
Subject(s) - calpain , neurotoxicity , glutamate receptor , spectrin , leupeptin , cerebellum , biology , biochemistry , nmda receptor , glutamic acid , chemistry , microbiology and biotechnology , toxicity , neuroscience , receptor , amino acid , cytoskeleton , enzyme , protease , organic chemistry , cell
Glutamate‐induced neurotoxicity and calpain activity were studied in primary cultures of rat cerebellar granule neurons and glial cells. Calpain activation, as monitored by quantitative immunoblotting of spectrin, required micromolar concentrations of Ca 2+ in neuronal homogenates (calpain I) and millimolar Ca 2+ concentrations in glial homogenates (calpain II). Glutamate‐induced toxicity and calpain activation were observed in neuronal, but not in glial, cultures. In neurons, calpain I activation by glutamate was dose‐dependent and persisted after withdrawal of neurotoxic doses of glutamate. Natural (GM1) and semisynthetic (LIGA4) gangliosides or the glutamate receptor blocker MK‐801 prevented calpain I activation and delayed neuronal death elicited by glutamate. GM1 and LIGA4 had no effect on calpain I activity in neuronal homogenates, however. Furthermore, two calpain I inhibitors (leupeptin and N ‐acetyl‐Leu‐Leu‐ norleucinal) prevented glutamate‐induced spectrin degradation, but failed to affect glutamate neurotoxicity. These results thus suggest that glutamate‐induced neurotoxicity is independent of calpain I activation.