Figure 5
Cilostazol alleviates Aβ-mediated disruption of lysosomal pH and activity in cultured cortical astrocytes. (a) Aβ induces lysosomal alkalization. Astrocytes were loaded with Aβ1–42 for 60 minutes and examined for DND-189 fluorescence (Scale bar, 20 μm). Whereas Aβ exposure markedly reduced DND-189 fluorescence (alkalization), addition of cilostazol (Aβ + Cilo) almost completely blocked the Aβ effect on lysosomal pH. Bars indicate relative changes in the fluorescence intensity. Values for individual bars were normalized to control values (mean ± SEM; n = 4; * denote P < 0.05, ** denote P < 0.01 compared with Aβ or Cilo; Two-tailed Student’s t-test for 2 comparisons). (b) Aβ decreases the activity of cathepsin B, a member of the lysosomal cysteine protease family. Fluorescence photomicrographs of cathepsin B-loaded astrocytes, before and after a 60-minute exposure to Aβ alone (Aβ) or Aβ plus cilostazol (Aβ + Cilo) comparisons (Scale bar, 20 μm). Aβ markedly reduced cathepsin B fluorescence in astrocytes, an effect that was reversed by addition of cilostazol. Bars indicate relative changes in the fluorescence intensity. Values for individual bars were normalized to control values (mean ± SEM; n = 4; * denote P < 0.05 compared with Aβ or Cilo; Two-tailed Student’s t-test for 2 comparisons).
