Figure 5
Glutamate decreases cdh1 and leads to glutaminase accumulation and apoptosis.
(a–d) Representative Western blot images of cdh1 and glutaminase (gls) under control conditions, with Aβ or glutamate (200 μM or 500 μM) (glu) treatment. Blots were quantified by densitometry and normalized against α-tubulin levels. The mean values ± SD of cdh1 (p < 0,05; p < 0,05) and gls (p < 0,01; p < 0,05) of three independent experiments of controls, Aβ and glutamate (500 μM) are shown. (e) Representative assays of flow cytometry analysis for apoptosis of neurons under control conditions, treated with glutamate (500 μM) or glutamate + GI. (f) Mean FITC values ± SD are shown from data of four independent experiments (p[C; Glut] < 0,01; p[Glut; Glut+GI] < 0,01). (g) Graphical representation of the Aβ- and glutamate-induced alterations. Ca2+ dysregulation cause cdk5-p25 stabilisation and this leads to cdh1 decrease. Glutaminase accumulates and generates an increase in extracellular glutamate levels, which might induce a positive feedback loop of further APC/C-Cdh1 deactivation.
