论文部分内容阅读
Aim:To observe the effects of sodium ferulate (SF) on amyloid beta (Aβ)_(1-40)-induced p38 mitogen-activated protein kinase (MAPK) signal transduction path-way and the neuroprotective effects of SF.Methods:Rats were injectedintracerebroventricularly with Aβ_(1-40).Six hours after injection,Western blottingwas used to determine the expressions of phosphorylated mitogen-activated pro-tein kinase kinase (MKK)3/MKK6,phospho-p38 MAPK,interleukin (IL)-1β,phospho-MAPK activating protein kinase 2 (MAPKAPK-2),the 27 kDa heat shockprotein (Hsp27),procaspase-9,-3,and-7 cleavage,and poly (ADP-ribose) poly-merase (PARP) cleavage.Seven days after injection,Nissl staining was used toobserve the morphological change in hippocampal CA1 regions.Results:Intracerebroventricular injection of Aβ_(1-40)induced an increase in phosphorylatedMKK3/MKK6 and p38 MAPK expressions in hippocampal tissue.These increases,in combination with enhanced interleukin (IL)-1β protein expression and reducedphospho-MAPKAPK2 and phospho-Hsp27 expression,mediate the Aβ-inducedactivation of cell death events as assessed by cleavage of procaspase-9,-3,and -7and caspase-3 substrate PARP cleavage.Pretreatment with SF (100 mg/kg and 200mg/kg daily,3 weeks) significantly prevented Aβ_(1-40)-induced increases in phos-phorylated MKK3/MKK6 and p38 MAPK expression.The Aβ_(1-40)-induced in-crease in IL-1β protein level was attenuated by pretreatment with SF.In addition,Aβ_(1-40)-induced decreases in phosphorylated MAPKAPK2 and Hsp27 expressionwere abrogated by administration of SF.In parallel with these findings,Aβ_(1-40)-induced changes in activation of caspase-9,caspase-7,and caspase-3 wereinhibited by pretreatment with SE Conclusion:SF prevents Aβ_(1-40)-induced neu-rotoxicity through suppression of MKK3/MKK6-p38 MAPK activity and IL-1expression 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 path-way and the neuroprotective effects of SF. Methods: Rats were injected intraterebroventricularly with Aβ_ (1-40). Six hours after injection, Western blotting was used to determine the expressions of phosphorylated mitogen-activated pro-tein kinase kinase (MKK) 3 / MKK6, phospho-p38 MAPK, interleukin (IL) , MAPK activating protein kinase 2 (MAPKAPK-2), the 27 kDa heat shock protein (Hsp27), procaspase-9, -3, and-7 cleavage, and poly (ADP- ribose) poly-merase (PARP) cleavage. Seven days after injection, Nissl staining was used toobserve the morphological change in hippocampal CA1 regions. Results: Intracerebroventricular injection of Aβ - (1-40) 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-MAPKAPK 2 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 Aβ_ (1-40) -induced increases in phos-phorylated MKK3 / MKK6 and p38 MAPK expression.The Aβ 1- (1-40) -induced in-crease in IL-1β protein level was attenuated by pretreatment with SF.In addition, Aβ_ (1-40) -induced decreases in phosphorylated MAPKAPK2 and Hsp27 expressionwere abrogated by administration of SF. In parallel with these findings, Aβ_ (1-40) -induced changes in activation of caspase-9, caspase -7, and caspase-3 were inhibited by pretreatment with SE Conclusion: SF prevents Aβ_ (1-40) -induced neu-rotoxicity through suppression of MKK3 / MKK6-p38 MAPK activity and IL-1 expression and upregulation of phospho-Hsp27 expression.