Effects of sodium ferulate on amyloid-beta-induced MKK3/MKK6-p38 MAPK-Hsp27 signal pathway and apoptosis in rat hippocampus  

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

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

出　　处：《Acta Pharmacologica Sinica》2006年第10期1309-1316,共8页中国药理学报（英文版）

基　　金：Project supported by Natural Science Foundation of Liaoning Province(No 20042171).

摘　　要：Aim： To observe the effects of sodium ferulate （SF） on amyloid beta （Aβ）1-40- induced p38 mitogen-activated protein kinase （MAPK） signal transduction pathway and the neuroprotective effects of SF. Methods： Rats were injected intracerebroventricularly with Aβ1-40. Six hours after injection, Western blotting was used to determine the expressions of phosphorylated mitogen-activated protein kinase kinase （MKK） 3/MKK6, phospho-p38 MAPK, interleukin （IL）-1 β, phospho-MAPK activating protein kinase 2 （MAPKAPK-2）, the 27 kDa heat shock protein （Hsp27）, procaspase-9, -3, and -7 cleavage, and poly （ADP-ribose） polymerase （PARP） cleavage. Seven days after injection, Nissl staining was used to observe the morphological change in hippocampal CA1 regions. Results： Intracerebroventricular injection of Aβ1-40 induced an increase in phosphorylated MKK3/MKK6 and p38 MAPK expressions in hippocampal tissue. These increases, in combination with enhanced interleukin （IL）- 1β protein expression and reduced phospho-MAPKAPK2 and phospho-Hsp27 expression, mediate the Aβ-induced activation of cell death events as assessed by cleavage of procaspase-9, -3, and -7 and caspase-3 substrate PARP cleavage. Pretreatment with SF （100 mg/kg and 200 mg/kg daily, 3 weeks） significantly prevented Aβ1-40-induced increases in phosphorylated MKK3/MKK6 and p38 MAPK expression. The Aβ1-40-induced increase in IL-1 β protein level was attenuated by pretreatment with SF. In addition, Aβ1-40induced decreases in phosphorylated MAPKAPK2 and Hsp27 expression were abrogated by administration of SE In parallel with these findings, Aβ1-40 induced changes in activation of caspase-9, caspase-7, and caspase-3 were inhibited by pretreatment with SE Conclusion： SF prevents Aβ1-40-induced neurotoxicity through suppression of MKK3/MKK6-p38 MAPK activity and IL-1β expression and upregulation of phospho-Hsp27 expression.Aim： To observe the effects of sodium ferulate （SF） on amyloid beta （Aβ）1-40- induced p38 mitogen-activated protein kinase （MAPK） signal transduction pathway and the neuroprotective effects of SF. Methods： Rats were injected intracerebroventricularly with Aβ1-40. Six hours after injection, Western blotting was used to determine the expressions of phosphorylated mitogen-activated protein kinase kinase （MKK） 3/MKK6, phospho-p38 MAPK, interleukin （IL）-1 β, phospho-MAPK activating protein kinase 2 （MAPKAPK-2）, the 27 kDa heat shock protein （Hsp27）, procaspase-9, -3, and -7 cleavage, and poly （ADP-ribose） polymerase （PARP） cleavage. Seven days after injection, Nissl staining was used to observe the morphological change in hippocampal CA1 regions. Results： Intracerebroventricular injection of Aβ1-40 induced an increase in phosphorylated MKK3/MKK6 and p38 MAPK expressions in hippocampal tissue. These increases, in combination with enhanced interleukin （IL）- 1β protein expression and reduced phospho-MAPKAPK2 and phospho-Hsp27 expression, mediate the Aβ-induced activation of cell death events as assessed by cleavage of procaspase-9, -3, and -7 and caspase-3 substrate PARP cleavage. Pretreatment with SF （100 mg/kg and 200 mg/kg daily, 3 weeks） significantly prevented Aβ1-40-induced increases in phosphorylated MKK3/MKK6 and p38 MAPK expression. The Aβ1-40-induced increase in IL-1 β protein level was attenuated by pretreatment with SF. In addition, Aβ1-40induced decreases in phosphorylated MAPKAPK2 and Hsp27 expression were abrogated by administration of SE In parallel with these findings, Aβ1-40 induced changes in activation of caspase-9, caspase-7, and caspase-3 were inhibited by pretreatment with SE Conclusion： SF prevents Aβ1-40-induced neurotoxicity through suppression of MKK3/MKK6-p38 MAPK activity and IL-1β expression and upregulation of phospho-Hsp27 expression.

关 键 词：ferulic acid amyloid MKK3/MKK6 p38mitogen-activated protein kinase INTERLEUKIN-1 27 kDa heat shock protein APOPTOSIS 

分 类 号：R74[医药卫生—神经病学与精神病学]