Effects of ibuprofen on amyloid β-protein fragment 1-40-induced p38 MAP kinase signal pathway and caspase cascades in rat hippocampus in vivo
- VernacularTitle:布洛芬对淀粉样β蛋白片段1～40引起的大鼠海马p38 MAP激酶信号传导通路及半胱氨酸天冬氨酸蛋白酶级联的影响
- Author:
Ying FAN
;
Ying JIN
;
Enzhi YAN
;
Jing YANG
;
Zhihong ZONG
;
Zhimin QI
- Publication Type:Journal Article
- Keywords:
ibuprofen;
amyloid beta-protein;
MAP kinase signaling system;
mitogen-activated protein kinase;
heat-shock proteins;
caspases
- From:
Chinese Journal of Pharmacology and Toxicology
2007;21(2):81-89
- CountryChina
- Language:Chinese
-
Abstract:
AIM To observe the neuroprotective effect and protective mechanisms of ibuprofen on amyloid β-protein fragment 1-40 (Aβ1-40)-induced neurotoxicity in rat hippocampus.METHODS Rats were given ibuprofen (15 mg·kg-1 daily,ig) for 3 weeks prior to icv single dose of Aβ1-40 (5 μL,1 mmol·L-1).Six hours after Aβ1-40 injection,Western blotting was used to determine the expressions of phospho-MAP kinase kinase (MKK)3/MKK6,phospho-p38 MAP kinase,phospho-MAP kinase activating protein kinase 2 (MAPKAPK2),heat-shock protein 27(Hsp27),procaspase 9,3,and 7 cleavage,and poly (ADP-ribose) polymerase (PARP) cleavage in hippocampal CA1 region.RESULTS Intracerebroventricular injection of Aβ1-40 induced an increase in phosphorylated MKK3/MKK6 and p38 MAP kinase expressions in hippocampal CA1.These increases,in combination with reduced phospho-MAPKAPK2 and phospho-Hsp27 expressions,mediated Aβ1-40-induced the activation of caspases cascades.Ibuprofen (15 mg·kg-1·d-1,3 weeks) significantly prevented Aβ1-40-induced increases in phosphorylated MKK3/MKK6 and p38 MAP kinase expressions.In addition,Aβ1-40-induced decreases in phosphorylated MAPKAPK2 and Hsp27 expressions were abrogated by ibuprofen.Aβ1-40-induced changes in activation of caspases cascades were inhibited by ibuprofen.CONCLUSIONIbuprofen prevents Aβ1-40-induced neurotoxicity through suppression of phosphorylated MKK3/MKK6 and p38 MAP kinase expressions and the up-regulation of phospho-Hsp27 expression.
