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. 2015 Jul 8;5:12059. doi: 10.1038/srep12059

Figure 2. Aβ generation and γ-secretase components are decreased in Agtr1a deficient mouse brain and fibroblasts.

Figure 2

(a) Effects of AT1a deficiency on ACE and neprilysin expression. (b) Determination of Aβ42 and Aβ40 levels in the brain cortex of 8-month-old hAPP/Agtr1a+/+, hAPP/Agtr1a+/− and hAPP/Agtr1a−/− mice by ELISA. n = 8 hAPP/Agtr1a+/+ mice, n = 9 hAPP/Agtr1a+/− mice and n = 4 hAPP/Agtr1a−/− mice. (c) Aβ40 and Aβ42 concentrations in the culture media of the primary cultured fibroblasts from hAPP/Agtr1a+/+, hAPP/Agtr1a+/− and hAPP/Agtr1a−/− mouse embryos. The Aβ40 and Aβ42 concentrations were normalized with the cellular protein amount. (d) Comparison of the γ-secretase components, PS1-CTF, NCT, Aph-1 and Pen-2, in the hAPP/Agtr1a+/+ and hAPP/Agtr1a−/− mouse brain lysate by immunoblot analysis (left panels). The relative levels of the γ-secretase components were determined by densitometry with normalization to β-actin (right panels). (e) Comparison of the γ-secretase components in the cell lysate of hAPP/Agtr1a+/+ and hAPP/Agtr1a−/− cells by immunoblot. (f) Amount of total cellular APP, β-CTF and α-CTF of APP (arrows) were determined by immunoblot analysis of APP. (g) sAPPα in the culture media of hAPP/Agtr1a+/+, hAPP/Agtr1a+/− and hAPP/Agtr1a−/− cells. Error bars show means ± s.e.m., n = 3–6 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 by one-way ANOVA followed by post hoc Bonferroni test comparing with hAPP/Agtr1a+/+ mouse. Cropped immunoblots are presented and all samples were compared under the same experimental conditions. The whole panels of the immunoblots are displayed in Supplemental Fig. 4 for full length PS1 and PS1-CTF in the 14-month-old mouse brain (Supplemental Fig. 4a), and for γ-secretase complex in the cell lysate of hAPP/Agtr1a+/+ and hAPP/Agtr1a−/− cells (Supplemental Fig. 4b).