Figure 6.

Liver lysosomes from buparlisib- or pictilisib-treated mice have increased CMA substrate uptake and decreased GFAP phosphorylation. (A and B) Lysosomes from buparlisib- and pictilisib-treated mice showed enhanced uptake of CMA substrate Tau, compared with lysosomes from solvent-treated control mice. (C) There was no difference in the fraction of broken lysosomes between the treatment groups, used for uptake assays shown in A and B. (D–F) GFAP phosphorylation was reduced on lysosomes from buparlisib- and pictilisib-treated mice, but total GFAP levels were not significantly changed. (D and G) Lysosomal HSPA8 levels were increased by both buparlisib and pictilisib treatment. P values written above brackets are derived from unpaired t tests. For each experiment, the buparlisib treatment group has lysosomes from three female and four male mice. The pictilisib and solvent control treatment groups have lysosomes from four female and four male mice each. Data from males and females were pooled, after showing no sex difference in the measured endpoints. Error bars are SEM. Bup, buparlisib; Pic, pictilisib; Prot. Inh., protease inhibitors; Sol, solvent.