Rebastinib inhibits FoxO1 activity and reduces dexamethasone-induced atrophy and its-related gene expression in cultured myotubes.

ABSTRACT: FoxO1, a transcription factor, is upregulated in skeletal muscle during atrophy and inactivation of FoxO1 is a potential strategy to prevent muscle loss. This study identified Rebastinib as a potent suppressor of FoxO1 activity among protein kinase inhibitors. To determine whether Rebastinib inhibits atrophy-related ubiquitin ligases gene expression and mitigates atrophy in mouse skeletal muscle-derived cells, we investigated its protective effects of the compound against dexamethasone (DEX)-induced muscle atrophy using C2C12 myotubes. Rebastinib inhibited the DEX-induced upregulation of atrogin-1 and MuRF-1 mRNA, and atrogin-1 protein. Rebastinib also suppressed protein degradation and increased myotube diameter in DEX-treated C2C12 myotubes. Additionally, Rebastinib ameliorated the DEX-

SUBMITTER: Sato T 

PROVIDER: S-EPMC11905838 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature