Figure 8. Calpain inhibition results in partial rescue of desmoplakin levels in homozygous DSP R451G engineered heart tissues.
(A) Engineered heart tissues were incubated with 25 μM of the calpain inhibitor MDL-28170(MDL) or a vehicle control (DMSO) for 72 hours and then probed for desmoplakin protein levels. Loading across gels was normalized by sarcomeric actin. (Gel images are representative of PGP1 MDL n = 10; PGP1 DMSO, n = 8; HO35 MDL, n = 8; HO35 DMSO, n = 8). (B) Quantification of immunoblot showing significant interaction between genotype and drug treatment (P < 0.05) as well as significant loss of DSP between genotype (*P < 0.05) and drug treatment for 2-way ANOVA with Tukey’s multiple comparisons test. While desmoplakin levels in WT/WT EHTs were significantly decreased in samples exposed to MDL, this decrease was not observed in R451G/R451G EHTs.