期刊
NEUROCHEMISTRY INTERNATIONAL
卷 62, 期 6, 页码 836-842出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2013.02.020
关键词
Glutamate; NMDA; Lectin; ConBr; PI3K/Akt; Neuroprotection
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil [305194/2010-0]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)/PROCAD
- CAPES/DGU [173/2008]
- National Institute of Science and Technology (INCT) for Excitotoxicity and Neuroprotection
- Fundacao de Amparo a Pesquisa de Santa Catarina (FAPESC)
- FAPESC/PRONEX - Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC)
- IBN.Net/CNPq
- CNPq
The excitotoxicity induced by excessive activation of the glutamatergic neurotransmission pathway is involved in several neuropathologies. In this sense, molecules that prevent the release of glutamate or the excessive activation of its receptors can be useful in preventing the neuronal cell death observed in these diseases. Lectins are proteins capable of reversible binding to the carbohydrates in glycoconjugates, and some have been used in the study and purification of glutamate receptors. ConBr is a mannose/glucose-binding lectin purified from Canavalia brasiliensis seeds. In the present study, we aimed to evaluate the neuroprotective activity of ConBr against glutamate-induced excitotoxicity. Hippocampal slices were isolated from adult male mice and incubated for 6 h in Krebs saline/DMEM buffer alone (control), in the presence of glutamate or glutamate plus ConBr. The phosphorylation of Akt and mitogen activated protein kinases (MAPKs) such as ERK1/2, p38(MAPK) and JNK1/2/3 was evaluated with western blotting. The results indicate that glutamate provoked a reduction in the hippocampal slice viability (-25%), diminished the phosphorylation of Akt and augmented p38(MAPK) and ERK1 phosphorylation. No changes were observed in the phosphorylation of JNK1/2/3 or ERK2. Notably, ConBr, through a mechanism dependent on carbohydrate interaction, prevented the reduction of cell viability and Akt phosphorylation induced by glutamate. Furthermore, in the presence of the PI3K inhibitor LY294002, ConBr was unable to reverse glutamate neurotoxicity. Taken together, our data suggest that the neuroprotective effect of ConBr against glutamate neurotoxicity requires oligosaccharide interaction and is dependent on the PI3K/Akt pathway. (C) 2013 Elsevier Ltd. All rights reserved.
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