Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action

被引:44
作者
Kreutz, Fernando [2 ]
Frozza, Rudimar L. [2 ]
Breier, Ana Carolina [2 ]
de Oliveira, Valeska A. [1 ]
Horn, Ana Paula [3 ]
Pettenuzzo, Leticia F. [1 ]
Netto, Carlos Alexandre [1 ,2 ]
Salbego, Christianne Gazzana [1 ,2 ]
Treis Trindade, Vera Maria [1 ,2 ]
机构
[1] Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, BR-90035003 Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Biol Bioquim, ICBS, BR-90035003 Porto Alegre, RS, Brazil
[3] Univ Fed Rio Grande, FURG, Inst Ciencias Biol, Setor Morfol, Rio Grande, RS, Brazil
关键词
Alzheimer's disease; Amyloid beta-peptide (A beta); Organotypic culture; Gangliosides; GM1; Neuroprotection; GSK3; beta; ORGANOTYPIC HIPPOCAMPAL CULTURES; OXYGEN-GLUCOSE DEPRIVATION; NEURONAL CELL-DEATH; ALZHEIMERS-DISEASE; SLICE CULTURES; PRECURSOR PROTEIN; RAT HIPPOCAMPUS; CEREBRAL-ISCHEMIA; NEONATAL HYPOXIA; TRK RECEPTORS;
D O I
10.1016/j.neuint.2011.06.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The effect of A beta 25-35 peptide, in its fibrillar and non-fibrillar forms, on ganglioside expression in organotypic hippocampal slice cultures was investigated. Gangliosides were endogenously labeled with D-[1-C-14] galactose and results showed that A beta 25-35 affected ganglioside expression, depending on the peptide aggregation state, that is, fibrillar A beta 25-35 caused an increase in GM3 labeling and a reduction in GD1b labeling, whereas the non-fibrillar form was able to enhance GM1 expression. Interestingly, GM1 exhibited a neuroprotective effect in this organotypic model, since pre-treatment of the hippocampal slices with GM1 10 mu M was able to prevent the toxicity triggered by the fibrillar A beta 25-35, when measured by propidium iodide uptake protocol. With the purpose of further investigating a possible mechanism of action, we analyzed the effect of GM1 treatment (1, 6, 12 and 24 h) upon the A beta-induced alterations on GSK3 beta dephosphorylation/activation state. Results demonstrated an important effect after 24-h incubation, with GM1 preventing the A beta-induced dephosphorylation (activation) of GSK3 beta, a signaling pathway involved in apoptosis triggering and neuronal death in models of Alzheimer's disease. Taken together, present results provide a new and important support for ganglioside participation in development of Alzheimer's disease experimental models and suggest a protective role for GM1 in A beta-induced toxicity. This may be useful for designing new therapeutic strategies for Alzheimer's treatment. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:648 / 655
页数:8
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