ARC Knockout Does Not Alter Apoptotic Enzyme Activities in Skeletal Muscle in Response to Angiotensin II Exposure

Abstract

Although apoptotic signalling does not cause complete skeletal muscle fiber elimination, apoptotic protease activation contributes to contractile protein degradation. The anti‐apoptotic protein apoptosis repressor with caspase recruitment domain (ARC) inhibits both intrinsic and extrinsic apoptotic pathways. Interestingly, although ARC expression levels are relatively high in mature skeletal muscle, its importance in mediating apoptotic signalling is underexplored. Therefore, the purpose of this study was to examine if ARC knockout (KO) would alter apoptotic enzyme activities in response to angiotensin II (AngII) exposure. Wild‐type (WT) and ARC KO mice were implanted with a subcutaneous placebo or AngII‐releasing pellet. No differences in caspase‐3, ‐8, or ‐9 activity were detected between groups in red gastrocnemius; however, a trend (p=0.07) towards an interaction effect was observed for calpain activity. In white gastrocnemius, there was a significant increase in caspase‐3 activity with AngII treatment; however, no differences were seen between genotypes. Although a trend (p=0.06) towards decreased caspase‐8 activity with AngII treatment was observed, no significant differences were detected. A significant decrease in caspase‐9 activity with AngII treatment was also observed. Finally, an interaction effect was detected for calpain activity. In conclusion, apoptotic enzyme activities are not increased in ARC KO compared to WT mice in response to AngII exposure. This may be due to adaptations occurring during development which may counteract the absence of ARC.