Figure 4.

Pharmacological activation of TRPML1 reduces ATZ accumulation in PiZ mouse livers

(A) Experimental plan for ML-SA5 treatment in PiZ mice; each arrow indicates an ML-SA5 administration and blood drops indicates timing of blood collections. (B) Liver PAS-D staining of vehicle- and ML-SA5-treated PiZ mice and relative quantifications (n = 7 per group). (C) Immunofluorescence for ATZ polymers on livers of vehicle- and ML-SA5-treated PiZ mice (n = 7 per group). (D) Immunoblot for soluble and insoluble fractions of livers from vehicle- or ML-SA5-treated PiZ mice and their quantifications (n = 3 per group). GAPDH and H3 were used as loading controls. (E) Changes in percentages of serum total AAT (n = 8 per group) and ATZ polymers (vehicle, n = 7; ML-SA5, n = 8) in PiZ mice. (F) Immunohistochemistry for TFEB in livers from wild-type or PiZ mice treated with vehicle or ML-SA5 (n = 3 per group). (G) Immunoblots for autophagy markers SQSTM1/p62 and LC3 in livers of wild-type (n = 3 per group) and PiZ mice (n = 5 per group) treated with vehicle or ML-SA5 and their relative quantifications. Vehicle and MLSA5 samples are on the same gel but are not contiguous. Data are shown as mean ± standard error. Student’s t test: ∗p value < 0.05; ∗∗p value < 0.01. A.U., arbitrary units; p.i., post-injection; WT, wild-type.