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. 2021 Jan 7;29(24):3945–3953. doi: 10.1093/hmg/ddaa248

Figure 4 .

Figure 4

Effect of ceramide biosynthesis inhibitors on mouse and human myoblasts. Expression levels of ubiquitin, TDP-43, p62, and LC3B autophagy markers were lower when treated with ceramide biosynthesis inhibitors (Myriocin at 0.25 μM, ARN14494 at 2 μM, L-cycloserine at 30 μM) in comparison to untreated VCP myoblasts (A, B). Treatment with ceramide degradation inhibitor (ARN082) resulted in similar TDP-43 and LC3B protein expression levels as untreated VCP myoblasts. Nuclear TDP-43 and cytoplasmic TDP-43 (C) including the densitometry results (D). (E) Myoblasts from VCPR155H/R155H homozygous mouse treated with the ceramide biosynthesis inhibitors, Myriocin (0.25 μM at 16 hours) or ARN14494 (2 μM at 16 hours), significantly decreased cellular levels of total ceramide and ceramide (d18:1/16:0). (F) Similar trends were also observed in the VCP patient-derived myoblasts treated with ARN14494, when compared with vehicle controls.***P < 0.001, **P < 0.01 and *P < 0.05 by one-way analysis of variance (ANOVA) with Dunnett’s multiple comparison post-test. ##P<0.01 compared with control group by two-way ANOVA with Turkey’s multiple comparison.