The complex of PAMAM-OH dendrimer with angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

Valeria Márquez-Miranda, Johanna Abrigo, Juan Carlos Rivera, Ingrid Araya-Durán, Javier Aravena, Felipe Simon, Nicolás Pacheco, Fernando Danilo González-Nilo, Claudio Cabello-Verrugio

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

Original languageEnglish
Pages (from-to)1985-1999
Number of pages15
JournalInternational Journal of Nanomedicine
Volume12
DOIs
Publication statusPublished - 13 Mar 2017

Keywords

  • Anti-atrophic peptide
  • Carrier
  • Muscle wasting
  • Peptide delivery

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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