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Metabotropic glutamate receptors prevent nitric oxide‐induced programmed cell death
Author(s) -
Vincent A.M.,
Mohammad Y.,
Ahmad I.,
Greenberg R.,
Maiese K.
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19971115)50:4<549::aid-jnr6>3.0.co;2-e
Subject(s) - metabotropic glutamate receptor , glutamate receptor , neuroprotection , microbiology and biotechnology , biology , programmed cell death , excitotoxicity , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 2 , neuroscience , signal transduction , chemistry , pharmacology , receptor , biochemistry , apoptosis
Activation of metabotropic glutamate receptor (mGluR) subtypes can prevent neuronal injury through the signal transduction pathways of nitric oxide (NO). It is this link to NO free radical injury and subsequent DNA damage that is the most intriguing. We therefore examined whether neuronal protection through mGluR activation was dependent on the molecular mechanisms of programmed cell death (PCD). The NO generators sodium nitroprusside and 3‐morpholino‐sydnonimine were administered to induce NO toxicity in primary hippocampal neurons. PCD was documented by hematoxylin and eosin nuclear staining, DNA gel electrophoresis, transmission electron microscopy, and protein synthesis assays. Following NO exposure, PCD induction was rapid and robust in approximately 70% of the neuronal population. Activation of specific mGluR subtypes with 1S,3R‐ACPD and L‐AP4, agents that are neuroprotective against NO, significantly limited the progression of PCD. In contrast, antagonism of mGluRs with L‐AP3 did not prevent the development of PCD. Induction of new protein synthesis, a common requisite for PCD, was evident following NO exposure, but did not appear to represent a principal pathway of modulation by the mGluR agonists. Our studies suggest that mGluR modulation of NO‐induced PCD represents a primary molecular pathway responsible for neuronal survival. Further elucidation of the molecular mGluR signaling pathways may yield new insight into specific genetic regulatory mechanisms responsible for neuronal injury. J. Neurosci. Res. 50: 549–564, 1997. © 1997 Wiley‐Liss, Inc.