Fig. 5
From: Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome
Identification of potential readouts for Nat10 inhibition in cells and tissues. a,b Representative images of western blots showing that 1 µM Remodelin treatment for 7 days decreases the high alpha-Tubulin (α-tubulin) K40 acetylation in HGPS-patient derived cells (a) and mouse tissues (b). In panel b NAT10 chemical (lane 3) or genetic (lane 4) inhibition reverses the high α-tubulin K40 acetylation levels in heart tissues from indicated mice; *indicates a cross-reacting band. We note that the ratio between Lamin A and C appears to vary between tissues. All western blotting experiments were performed independently at least three times (n ≥ 3/genotype). c Representative immunofluorescence images of acetyl-α-tubulin K40 in HGPS-patient derived cells, as compared to matching healthy fibroblasts. Scale bar = 20 µm. The K40 α-tubulin acetylation (magenta) is increased in the HGPS-patient derived cells and decreased upon Remodelin treatment. d Representative immunofluorescence images (left) and quantification (right) of acetyl-α-tubulin K40 in aortas of terminal mice of the indicated genotypes and treatments. Scale bar = 10 µm. The K40 α-tubulin acetylation (green; white arrowheads point to example of cells that show increased K40 acetylation) is increased in LmnaG609G/G609G mice and significantly decreased in such mice, upon Remodelin treatment (n = 3; mean ± s.d.; individual data points represented; n.s. not significant, *p < 0.05; **p < 0.01, ***p < 0.001; two-tailed Student’s t-test). For better visualization, these are higher magnification snapshots (red dotted squares) from images in Supplementary Fig. 9d. Quantification was performed on full size aorta images from n = 3 independent mice
