Sodium ferulate prevents amyloid-beta-induced neurotoxicity through suppression of p38 MAPK and upregulation of ERK-1/2 and Akt/protein kinase B in rat hippocampus  

作　　者：Ying JIN En-zhi YAN Ying FAN Zhi-hong ZONG Zhi-min QI Zhi LI 

机构地区：[1]Department of Ethnopharmacology, China Medical University, Shengyang 110001 [2]Department of Pharmacology, Jinzhou Medical College, Jinzhou 121001, China [3]Department of Biochemistry, China Medical University, Shengyang 110001, China

出　　处：《Acta Pharmacologica Sinica》2005年第8期943-951,共9页中国药理学报（英文版）

基　　金：Natural Science Foundation of Liaoning Province (№ 20042171)

摘　　要：Aim： To observe whether an amyloid β （Aβ）-induced increase in interleukin （IL）-1β was accompanied by an increase in the p38 mitogen-activated protein kinase（MAPK） pathway and a decrease in the cell survival pathway, and whether sodium ferulate （SF） treatment was effective in preventing these Aβ-induced changes.Methods： Rats were injected intracerebroventricularly with Aβ25-35. Seven days after injection, immunohistochemical techniques for glial fibrillary acidic protein（GFAP） were used to determine the astrocyte infiltration and activation in hippocampal CA1 areas. The expression of IL-1β, extracellular signal-regulated kinase（ERK）, p38 MAPK, Akt/protein kinase B （PKB）, Fas ligand and caspase-3 were determined by Western blotting. The caspase-3 activity was measured by cleavage of the caspase-3 substrate （Ac-DEVD-pNA）. Reverse transcriptionpolymerase chain reaction was used to analyze the changes in IL- 1β mRNA levels.Results：Intracerebroventricular injection of Aβ25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized byincreased IL-1β production and elevated levels of IL- 1β mRNA. Increased IL-1β synthesis was accompanied by increased activation of p38 MAPK and downregulation of phospho-ERK and phospho-Akt/PKB in hippocampal CA regions prepared from Aβ-treated rats, leading to cell death as assessed by activation of caspase-3. SF significantly prevented Aβ-induced increases in IL- 1β and p38 MAPK activation and also Aβ-induced changes in phospho-ERK and phospho-Akt/PKB expression levels. Conclusion： SF prevents Aβ-induced neurotoxicity through suppression of p38 MAPK activation and upregulation of phospho-ERK and phospho-Akt/PKB expression.Aim： To observe whether an amyloid β （Aβ）-induced increase in interleukin （IL）-1β was accompanied by an increase in the p38 mitogen-activated protein kinase（MAPK） pathway and a decrease in the cell survival pathway, and whether sodium ferulate （SF） treatment was effective in preventing these Aβ-induced changes.Methods： Rats were injected intracerebroventricularly with Aβ25-35. Seven days after injection, immunohistochemical techniques for glial fibrillary acidic protein（GFAP） were used to determine the astrocyte infiltration and activation in hippocampal CA1 areas. The expression of IL-1β, extracellular signal-regulated kinase（ERK）, p38 MAPK, Akt/protein kinase B （PKB）, Fas ligand and caspase-3 were determined by Western blotting. The caspase-3 activity was measured by cleavage of the caspase-3 substrate （Ac-DEVD-pNA）. Reverse transcriptionpolymerase chain reaction was used to analyze the changes in IL- 1β mRNA levels.Results：Intracerebroventricular injection of Aβ25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized byincreased IL-1β production and elevated levels of IL- 1β mRNA. Increased IL-1β synthesis was accompanied by increased activation of p38 MAPK and downregulation of phospho-ERK and phospho-Akt/PKB in hippocampal CA regions prepared from Aβ-treated rats, leading to cell death as assessed by activation of caspase-3. SF significantly prevented Aβ-induced increases in IL- 1β and p38 MAPK activation and also Aβ-induced changes in phospho-ERK and phospho-Akt/PKB expression levels. Conclusion： SF prevents Aβ-induced neurotoxicity through suppression of p38 MAPK activation and upregulation of phospho-ERK and phospho-Akt/PKB expression.

关 键 词：ferulic acid amyloid INTERLEUKIN-1 p38 mitogen-activated protein kinases extracellular signal-regulated kinases protooncogene proteins c-akt Alzheimer disease 

分 类 号：R741[医药卫生—神经病学与精神病学]