Analysis of eIF5A in the context of insulin sensitivity

Abstract

The eukaryotic translation initiation factor 5A (eIF5A) is highly conserved in archaea and eukaryotes, and is the only protein containing the amino acid residue hypusine, which is required for its activity. eIF5A has been involved in different points of the gene expression control, such as transcription, nuclear pore transport, nonsense-mediated decay (NMD), and translation. In addition, eIF5A has also been associated to important cellular and physiological process, such as cellular proliferation, differentiation, apoptosis, embryogenesis and development. In the context of muscular physiology, can be highlight the involvement of eIF5A on the skeletal muscle stem cell (satellite cells) proliferation and differentiation. These process are essentials for muscle development and regeneration; conditions in which insulin is a key hormone. However, eIF5A is also considered a critical factor for some pathological conditions, such as cancer, inflammation, diabetes and viral replication. So, eIF5A can be considered a challenger therapeutic target, because it is expected that any interference in the expression of eIF5A or its hypusination, in an unguided manner (without cellular or tissue specificity), have potential for adverse effects. Due to the beneficial and malignant characteristics of eIF5A the study of the control of its expression and activity is important for the establishment of safe and effective therapeutic strategies based on eIF5A metaboslim. Unpublished data (attached 1) from our group revealed that insulin has positive modulatory effects on eIF5A expression in rat L6 myoblasts cells. However, the molecular events associated to this process still have to be clarified. In this context, the present proposal presents two aims: (I) to contribute to the characterization of a peptide fraction derived from salmon that was able to increase insulin sensitivity, a finding obtained by Dr. Marette group and (II) to verify whether the salmon-derived peptides have a positive effect on insulin-induced expression of eIF5A. If this is the case, the salmon peptides could be explored as a future strategy to suppress adverse effects associated the inhibition of eIF5A on undesired target tissues.