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• W2081383833 abstract "Glycogen synthase kinase (GSK)-3β and extracellular signal-regulated kinase (ERK) regulate several cellular signaling pathways in common, including embryonic development, cell differentiation and apoptosis. In this study, we investigated whether GSK-3β inhibition is involved in ERK activation, which affects the activation of NF-κB and induction of MMP-9 in cultured rat primary astrocytes. Here, we found that GSK-3β inhibition using GSK-3β inhibitor TDZD-8 increased the phosphorylation of GSK-3β at Ser9 site as well as the phosphorylation of ERK1/2 and Akt at Ser473 site. In this condition, GSK-3β inhibition increased MMP-9 but not MMP-2 activity in a concentration-dependent manner. In RT-PCR analysis, MMP-9 mRNA level was increased by GSK-3β inhibition in a concentration-dependent manner. MMP-9 promoter reporter activity was similarly increased by GSK-3β inhibition. Pretreatment of U-0126 (MEK1/2 inhibitor) completely abolished the GSK-3β inhibition-induced phosphorylation of ERK1/2. U-0126 prevented GSK-3β inhibition-mediated induction of MMP-9 reporter activity as well as the MMP-9 gene expression. The transcriptional activity of NF-κB was significantly increased by GSK-3β inhibition, which was determined by nuclear translocation of NF-κB. Inhibition of ERK1/2 activity by U-0126 also completely blocked the nuclear translocation of NF-κB. Transfection of dominant negative plasmid (S9A) of GSK-3β significantly decreased phosphorylation of ERK, MMP-9 expression and nuclear translocation of NF-κB by GSK-3β inhibition as compared to wild type GSK-3β. These data suggest that GSK-3β inhibition mediates ERK1/2 activation followed by NF-κB activation, which directly regulates the induction of MMP-9 in rat primary astrocytes." @default.
• W2081383833 created "2016-06-24" @default.
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• W2081383833 date "2007-12-01" @default.
• W2081383833 modified "2023-10-13" @default.
• W2081383833 title "Inhibition of GSK-3β mediates expression of MMP-9 through ERK1/2 activation and translocation of NF-κB in rat primary astrocyte" @default.
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• W2081383833 doi "https://doi.org/10.1016/j.brainres.2007.10.018" @default.
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