NDLI: Molecular Alterations Associated with the NMDA Preconditioning-Induced Neuroprotective Mechanism Against Glutamate Cytotoxicity

Content Provider	Springer Nature Link
Author	Sragovich, Shlomo Bromberg, Yael Sperling, Oded Zoref Shani, Esther
Copyright Year	2011
Abstract	Exposure of the brain to sub-lethal concentrations of glutamate activates, through stimulation of the glutamate N-methyl-d-aspartate (NMDA) receptors, an endogenous brain protective mechanism (NMDA preconditioning) against glutamate cytotoxicity and various other injurious stimuli. Selective drug activation of this mechanism is considered to be a promising neuroprotective treatment against the devastating consequences of stroke and other traumatic brain insults. Although some properties of this mechanism have been characterized, many aspects concerning it are yet to be elucidated. In order to improve our understanding of the NMDA preconditioning mechanism, we have established an experimental in vitro model of primary rat neuronal cultures, in which NMDA preconditioning completely abolishes the glutamic acid insult-induced neuronal damage. Employing this model, we have monitored in the present study the level of activation or expression of several signal transducing proteins, assumed to be involved in the NMDA-activated protective mechanism, at various time points during the three successive periods of the model, preconditioning, insult, and reperfusion. The results demonstrated that the NMDA preconditioning-induced neuroprotective mechanism is associated with inactivation of p66ShcA, prevention of the insult-induced inactivation of Src, activation of AKT, inactivation followed by reactivation of FKHR-L1, and with increased expression of p52ShcA, EGFR, and MnSOD. The essential role of Src activity in the protective mechanism was further indicated by the demonstration that decreasing Src activation level by the Src inhibitor PP2 attenuated the NMDA preconditioning-induced protection. The alterations detailed above in the activation status or level of expression of the studied proteins are suggested to be part of the NMDA preconditioning-induced neuroprotective mechanism.
Starting Page	519
Ending Page	532
Page Count	14
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	47
Issue Number	3
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2011-11-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Glutamic acid cytotoxicity Neuroprotection NMDA preconditioning ROS Proteomics Neurosciences Neurology Cell Biology Neurochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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