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• W3033826577 abstract "Abstract UBR5 is an E3-ubiquitin-ligase positively associated with anabolism, hypertrophy and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to investigate the mechanism of action of UBR5 by silencing the UBR5 gene in-vitro and in-vivo. The siRNA-induced reduction (−77%) in UBR5 gene expression in human myotubes was prevented by mechanical loading, suggesting that UBR5 gene expression was activated downstream of mechano-transduction signalling. MEK/ERK/p90S6K-signalling is an established mechano-sensitive-pathway involved in muscle anabolism/hypertrophy and importantly, has been shown to regulate UBR5 during growth of cancer cells. Therefore, we electroporated a UBR5 RNAi plasmid into mouse Tibialis Anterior muscle in-vivo to investigate the impact of reduced UBR5 on MEK/ERK/p90RSK-signalling. Electroporation resulted in a 55%/60% reduction in UBR5 mRNA/protein. Seven days post electroporation, while overall muscle mass was not significantly reduced, mean fibre CSA of GFP-positive fibres was reduced (−9.5%) and the number of large fibres were lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis (puromycin incorporation) and ERK1/2-phosphorylation. However, p90RSK-phosphorylation significantly increased, suggesting a potential compensatory mechanism following a reduction in UBR5. Finally, these acute changes evident after 7 days of UBR5 knockdown were exacerbated after 30 days, culminating in significant reductions in muscle mass (−4.6%) and fibre CSA (−18.5%). The present study supports the notion that UBR5 plays an important role in muscle anabolism/hypertrophy, and that a reduction in UBR5 is associated with alterations in ERK1/2 and p90RSK that culminates in atrophy." @default.
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• W3033826577 date "2020-06-06" @default.
• W3033826577 modified "2023-09-27" @default.
• W3033826577 title "UBR5 knockdown in human myotubes in-vitro and mouse skeletal muscle tissue in-vivo determines its pertinent role in anabolism and hypertrophy" @default.
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