Involvement of eukaryotic translation initiation factor 5A (eIF5A) in skeletal muscle stem cell differentiation

Abstract

The protein eIF5A is involved in different steps of mRNA metabolism. This factor contains a special amino acid residue named hypusine. Hypusine is required for the eIF5A activity being produced by a post‐translational modification involving spermidine as substrate. Stem cells (satellite cells) from skeletal muscle rats were submitted to differentiation and an increase of eIF5A gene expression was observed. An increased content of eIF5A protein was observed in satellite cells on differentiation in comparison to non‐differentiated satellite cells and muscle tissue. The treatment with GC7, a hypusination inhibitor, abolished the differentiation process. In association with the differentiation blockage, an increase in glucose consumption and lactate production and a decrease in glucose and palmitate decarboxylation were observed. Also, there was a reduction in cell proliferation and protein synthesis. L‐arginine, a partial suppressor of muscle dystrophic phenotype and spermidine precursor, partially abolished the GC7 effects. Our results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle differentiation.Supported by: FAPESP, CNPq and CAPES.