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Neuroprotection by sodium ferulate against glutamate-induced apoptosis is mediated by ERK and PI3 kinase pathways.

Abstract：

AIM:To investigate whether sodium ferulate (SF) can protect cortical neurons from glutamate-induced neurotoxicity and the mechanisms responsible for this protection. METHODS:Cultured cortical neurons were incubated with 50 micromol/L glutamate for either 30 min or 24 h, with or without pre-incubation with SF (100, 200, and 500 micromol/L, respectively). LY294002, wortmannin, PD98059, and U0126 were added respectively to the cells 1 h prior to SF treatment. After incubation with glutamate for 24 h, neuronal apoptosis was quantified by scoring the percentage of cells with apoptotic nuclear morphology after Hoechst 33258 staining. After incubation with glutamate for either 30 min or 24 h, cellular extracts were prepared for Western blotting of active caspase-3, poly (ADP-ribose) polymerase (PARP), mu-calpain, Bcl-2, phospho-Akt, phosphorylated ribosomal protein S6 protein kinase (p70S6K), phospho-mitogen-activated protein kinase kinase (MEK1/2) and phosphorylated extracellular signal-regulated kinase (ERK) 1/2. RESULTS:SF reduced glutamate-evoked apoptotic morphology, active caspase-3 protein expression, and PARP cleavage and inhibited the glutamate-induced upregulation of the mu-calpain protein level. The inhibition of the phosphatidylinositol 3-kinase (PI3K) and the MEK/ERK1/2 pathways partly abrogated the protective effect of SF against glutamate-induced neuronal apoptosis. SF prevented the glutamate-induced decrease in the activity of the PI3K/Akt/p70S6K and the MEK/ERK1/2 pathways. Moreover, incubation of cortical neurons with SF for 30 min inhibited the reduction of the Bcl-2 expression induced by glutamate. CONCLUSION:The results indicate that PI3K/Akt/p70S6K and the MEK/ERK signaling pathways play important roles in the protective effect of SF against glutamate toxicity in cortical neurons.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Jin Y,Yan EZ,Fan Y,Guo XL,Zhao YJ,Zong ZH,Liu Z

doi

10.1111/j.1745-7254.2007.00634.x

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1881-90

issue

eissn

1671-4083

issn

1745-7254

journal_volume

pub_type

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Neuroprotection by sodium ferulate against glutamate-induced apoptosis is mediated by ERK and PI3 kinase pathways.