1. Aβ-mediated Ras-MAPK signaling and Cyclin D1 expression in B103 cells are dependent on APP expression and can be reversed with MEK or Ras inhibition.
Aβ-mediated Ras-MAPK signaling and Cyclin D1 expression in B103 cells are dependent on APP expression and can be reversed with MEK or Ras inhibition. Initial studies were conducted with B cells to determine the concentration of the inhibitors required to inhibit ERK or Ras. A, Treatment with 10 μm U0126 or 5 μm tipifarnib for 24 h showed unfarnesylation of Ras (U-Ras) on treatment with tipifarnib but not with U0126. Both U0126 and tipifarnib inhibited ERK activation and Cyclin D1 expression. Total ERK and actin were used for normalization of blots. Data shown is in duplicate and is representative of four independent experiments. B, B103 and B cells were treated with or without 2.5 μm Aβ, in the presence or absence of MEK inhibitor U0126 for 24 h, and samples were analyzed for changes in P-ERK, ERK, Cyclin D1, and Ras by Western blot. Protein was normalized to levels of Actin. Quantification of data for P-ERK (C), Cyclin D1 (D), and Ras (E) are shown in respective bar graphs. Data from three independent experiments is shown. Statistical analysis was performed using ANOVA. The data represent the mean ± SEM; p < 0.05.
Lisa Kirouac et al. eNeuro 2017;4:ENEURO
©2017 by Society for Neuroscience