@article{APS4593,
author = {Ying Jin and Ying Fan and En-zhi Yan and Zhuo Liu and Zhi-hong Zong and Zhi-min Qi},
title = {Effects of sodium ferulate on amyloid-beta-induced MKK3/MKK6-p38 MAPK-Hsp27 signal pathway and apoptosis in rat hippocampus},
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {10},
year = {2016},
keywords = {},
abstract = {Aim: To observe the effects of sodium ferulate (SF) on amyloid beta (Abeta)1–40 induced p38 mitogen-activated protein kinase (MAPK) signal transduction pathway and the neuroprotective effects of SF.
Methods: Rats were injected intracerebroventricularly with Abeta1–40. 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)-1beta, 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 Abeta1–40 induced an increase in phosphorylated MKK3/MKK6 and p38 MAPK expressions in hippocampal tissue. These increases, in combination with enhanced interleukin (IL)-1beta protein expression and reduced phospho-MAPKAPK2 and phospho-Hsp27 expression, mediate the Abeta-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 Abeta1–40-induced increases in phosphorylated MKK3/MKK6 and p38 MAPK expression. The Abeta1–40-induced increase in IL-1beta protein level was attenuated by pretreatment with SF. In addition, Abeta1–40-induced decreases in phosphorylated MAPKAPK2 and Hsp27 expression were abrogated by administration of SF. In parallel with these findings, Abeta1–40-induced changes in activation of caspase-9, caspase-7, and caspase-3 were inhibited by pretreatment with SF.
Conclusion: SF prevents Abeta1–40-induced neurotoxicity through suppression of MKK3/MKK6-p38 MAPK activity and IL-1beta expression and upregulation of phospho-Hsp27 expression.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4593}
}