אילמ"ר - האיגוד הישראלי למדעי המעבדה הרפואית

אילמ"ר - האיגוד הישראלי למדעי המעבדה הרפואית

כינוס שנתי ה-46 | 2012

פוסטרים להצגה בכינוס

Molecular Alterations Associated with the NMDA Preconditioning-Induced Neuroprotective Mechanism against Glutamate Cytotoxicity

Shlomo Sragovich, Hila Navon, Yael Bromberg, Oded Sperling, Esther Zoref-Shani
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel, 69978.

 

Background: Stroke is the third leading cause of death in the western countries and many survivors suffer from devastating consequences, but means to effectively prevent or lessen the stroke-induced brain damage are yet to be developed. Potent future neuroprotective drugs may exert protection through activation of endogenous neuroprotective mechanisms. The N-methyl-D-aspartate (NMDA) preconditioning mechanism is a major endogenous brain protective mechanism, however the mechanism by which it exerts protection is not yet fully clarified.
The aim of this study was to further elucidate the mechanism of NMDA preconditioning in order to facilitate future development of effective neuroprotective drugs.                   

Methods: An experimental model of primary rat neuronal cultures was established for this purpose: The cultures are exposed to preconditioning by NMDA (50 µM, 18 h) followed by exposure to glutamate insult (200 µM, 1 h), followed by reperfusion for 24 h. The level of activity or expression of surmised involved signal transducing proteins was monitored during these periods.

Results: NMDA preconditioning was found to be associated with activation of ERK 1/2 and of AKT and with inactivation of JNK and of p66ShcA. In addition it was found to be associated with prevention of the insult-induced inactivation of CREB and of Src. The preconditioning resulted also in inactivation followed by reactivation of FKHR-L1 and by increased expression of p52ShcA, EGFR and MnSOD.

Conclusions: The NMDA preconditioning-induced alterations in the activation or expression level observed in the above signal transducing proteins are probably part of the NMDA preconditioning-induced protective mechanism. How these alterations are induced by the sublethal activation of the NMDA receptors (preconditioning); which signaling pathways are activated or inhibited by these alterations and how they lead to the acquisition of protection against glutamate cytotoxicity is still to be clarified.

This study was supported in part by the Herman Shouder Research Fund, Sackler Faculty of Medicine, Tel-Aviv University

1. Navon, H., Bromberg, Y., Sperling, O., Zoref-Shani, E., Neuroprotection by NMDA preconditioning against glutamate cytotoxicity is mediated through activation of ERK 1/2, inactivation of JNK and by prevention of glutamate-induced CREB inactivation. Journal of Molecular Neuroscience , 46,100-8, 2012
2. Sragovich, S., Bromberg, Y., Sperling, O., Zoref-Shani, E., Molecular alterations associated with the NMDA preconditioning-induced neuroprotective mechanism against glutamate cytotoxicity. Journal of Molecular Neuroscience , In press, 2012

 

לתכנית הכנס     חזרה לריכוז הפוסטרים 2012
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