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MGLuR5 activation reduces β‐amyloid‐induced cell death in primary neuronal cultures and attenuates translocation of cytochrome c and apoptosis‐inducing factor
Author(s) -
Movsesyan Vilen A.,
Stoica Bogdan A.,
Faden Alan I.
Publication year - 2004
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.1471-4159.2004.02451.x
Subject(s) - metabotropic glutamate receptor 5 , staurosporine , neuroprotection , apoptosis , biology , cytochrome c , glutamate receptor , agonist , neurotoxicity , pharmacology , metabotropic glutamate receptor , caspase , caspase 3 , microbiology and biotechnology , programmed cell death , protein kinase c , medicine , biochemistry , receptor , signal transduction , toxicity
Abstract Activation of metabotropic glutamate receptor 5 (mGluR5) has been shown to reduce caspase‐dependent apoptosis in primary neuronal cultures induced by staurosporine and etoposide. β‐Amyloid (Aβ)‐induced neurotoxicity in culture appears to be in part caspase mediated. In the present studies the effects of treatment with an mGluR5 agonist or antagonist on Aβ‐induced neuronal apoptosis were examined in rat cortical neuronal cultures. Pretreatment with the selective mGluR5 agonist ( RS )‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) markedly reduced the number of apoptotic cells after exposure to Aβ (25–35), as well as associated LDH release. Blockade of mGluR5 by the selective antagonist, 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP) attenuated these effects of CHPG. A similar neuroprotective effect of mGluR5 activation by CHPG was observed in cultures treated with full‐length Aβ peptide (1–42). CHPG attenuated Aβ (25–35)‐induced cytochrome c release and decreased levels of active caspase‐3 protein. CHPG also reduced translocation of apoptosis‐inducing factor (AIF) induced by Aβ (25–35). Thus, mGluR5 activation limits the release of mitochondrial proteins associated with induction of both caspase‐dependent and ‐independent apoptosis.