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Insulin action on protein synthesis and its association with eIF5A expression and hypusination

  • André Ricardo Gomes de Proença
  • Karina Danielle Pereira
  • Leticia Meneguello
  • Leticia Tamborlin
  • Augusto Ducati Luchessi
Original Article
  • 51 Downloads

Abstract

The hormone insulin plays a central role in the metabolism of carbohydrates, lipids, and proteins. In relation to protein metabolism, insulin stimulates amino acid uptake and activates protein synthesis in responsive cells by modulation of signal transduction pathways, such as associated to Akt/PkB, mTOR, S6Ks, 4E-BP1, and several translation initiation/elongation factors. In this context, there is no information on direct cellular treatment with insulin and effects on eukaryotic translation initiation factor 5A (eIF5A) regulation. The eIF5A protein contains an exclusive amino acid residue denominated hypusine, which is essential for its activity and synthesized by posttranslational modification of a specific lysine residue using spermidine as substrate. The eIF5A protein is involved in cellular proliferation and differentiation processes, as observed for satellite cells derived from rat muscles, revealing that eIF5A has an important role in muscle regeneration. The aim of this study was to determine whether eIF5A expression and hypusination are influenced by direct treatment of insulin on L6 myoblast cells. We observed that insulin increased the content of eIF5A transcripts. This effect occurred in cells treated or depleted of fetal bovine serum, revealing a positive insulin effect independent of other serum components. In addition, it was observed that hypusination follows the maintenance of eIF5A protein content in the serum depleted cells and treated with insulin. These results demonstrate that eIF5A is modulated by insulin, contributing the protein synthesis machinery control, as observed by puromycin incorporation in nascent proteins.

Keywords

Myoblast cells Insulin Protein synthesis eIF5A Hypusine 

Notes

Acknowledgements

We are grateful to São Paulo Research Foundation (FAPESP) for the financial support. We would like to thank Dr. Rui Curi (USP, Brazil) for L6 cells, Dr. Fernando M. Simabuco (UNICAMP, Brazil) for puromycin and mouse monoclonal anti-puromycin; Dr. Raghavendra G. Mirmira and Dr. Bernhard Maier (IU School of Medicine, USA) for rabbit polyclonal anti-hypusine antibody (IU-88); Dr. Sandro R. Valentini (UNESP, Brazil) for GC7, spermidine and aminoguanidine.

Author contributions

ADL conceived and supervised the study; ADL and ARGP designed the experiments; ARGP, KDP, LM, and LT performed the experiments; ADL, ARGP, KDP, LM, and LT analyzed the data, interpreted the results and wrote the manuscript.

Funding

This work was supported by Grant 2010/18095-0 from the São Paulo Research Foundation (FAPESP). A.R.G.P., K.D.P, L.M, and L.T are recipients of FAPESP scholarships 2013/20504-3, 2013/23620-4, 2014/27154-0 and 2017/21914-1 respectively.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Laboratory of Biotechnology, School of Applied SciencesUniversity of Campinas (UNICAMP)LimeiraBrazil
  2. 2.Institute of BiosciencesSão Paulo State University (UNESP)Rio ClaroBrazil
  3. 3.Laboratório de Biotecnologia, Faculdade de Ciências AplicadasUniversidade Estadual de CampinasLimeiraBrazil

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