RGD Reference Report - Effects of sodium ferulate on amyloid-beta-induced MKK3/MKK6-p38 MAPK-Hsp27 signal pathway and apoptosis in rat hippocampus. - Rat Genome Database

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

Authors: Jin, Y  Fan, Y  Yan, EZ  Liu, Z  Zong, ZH  Qi, ZM 
Citation: Jin Y, etal., Acta Pharmacol Sin. 2006 Oct;27(10):1309-16.
RGD ID: 1582278
Pubmed: PMID:17007737   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1745-7254.2006.00414.x   (Journal Full-text)

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.

Objects referenced in this article
Gene Map2k3 mitogen activated protein kinase kinase 3 Rattus norvegicus
Gene Map2k6 mitogen-activated protein kinase kinase 6 Rattus norvegicus

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