Proteomic Analysis of the Mice Hippocampus After Preconditioning Induced by N -Methyl- d -Aspartate (NMDA)
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Proteomic Analysis of the Mice Hippocampus After Preconditioning Induced by N-Methyl-D-Aspartate (NMDA) Gabrielle do Amaral e Silva Müller & Samuel Vandresen-Filho & Carolina Pereira Tavares & Angela C. O. Menegatti & Hernán Terenzi & Carla Inês Tasca & Patricia Cardoso Severino
Received: 23 July 2012 / Accepted: 11 September 2012 / Published online: 22 September 2012 # Springer Science+Business Media, LLC 2012
Abstract Preconditioning induced by N-methyl-D-aspartate (NMDA) has been used as a therapeutic tool against later neuronal insults. NMDA preconditioning affords neuroprotection against convulsions and cellular damage induced by the NMDA receptor agonist, quinolinic acid (QA) with time-window dependence. This study aimed to evaluate the molecular alterations promoted by NMDA and to compare these alterations in different periods of time that are related to the presence or lack of neuroprotection. Putative mechanisms related to NMDA preconditioning were evaluated via a proteomic analysis by using a time-window study. After a subconvulsant and protective dose of NMDA administration mice, hippocampi were removed (1, 24 or 72 h) and total protein analyzed by 2DE gels and identified by MALDI-TOF. Differential protein expression among the time induction of NMDA preconditioning was observed. In the hippocampus of protected mice (24 h), four proteins: HSP70(B), aspartyl-tRNA synthetase, phosphatidylethanolamine binding protein and creatine kinase were found to be up-regulated. Two other proteins, HSP70(A) and V-type proton ATPase were found down-regulated. Proteomic analysis showed that the neuroprotection induced by NMDA preconditioning altered signaling pathways, cell energy G. do Amaral e Silva Müller : C. P. Tavares : A. C. O. Menegatti : H. Terenzi Centro de Biologia Molecular Estrutural, Departamento de Bioquímica, Universidade Federal de Santa Catarina, CEP 88040-900, Florianópolis, SC, Brazil S. Vandresen-Filho : C. I. Tasca : P. C. Severino (*) Laboratório de Neuroquímica 4, Departamento de Bioquímica, CCB, UFSC, CEP 88040-900 Florianópolis, SC, Brazil e-mail: [email protected]
maintenance and protein synthesis and processing. These events may occur in a sense to attenuate the excitotoxicity process during the activation of neuroprotection promoted by NMDA preconditioning. Keywords Brain proteome . Hippocampus proteome . NMDA preconditioning . Neuroprotection
Introduction Brain preconditioning or tolerance refers to a state of transient brain resistance to a lethal insult achieved by a prior mild insult (Rejdak et al. 2001). The preconditioning generates a state of cell, tissue or whole organism protection against lethal insults. Low doses of N-methyl-D-aspartate (NMDA) have been shown to promote neuroprotection in vitro (Chuang et al. 1992; Dickie et al. 1996; Arthur et al. 2004; Boeck et al. 2005) and in vivo (Boeck et al. 2004; Miao et al. 2005) against several brain insults. In all conditions studied, the neuroprotective effects of NMDA was time and concentration-dependent, suggesting that dose and time
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