TY - JOUR
T1 - The complex of PAMAM-OH dendrimer with angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice
AU - Márquez-Miranda, Valeria
AU - Abrigo, Johanna
AU - Rivera, Juan Carlos
AU - Araya-Durán, Ingrid
AU - Aravena, Javier
AU - Simon, Felipe
AU - Pacheco, Nicolás
AU - González-Nilo, Fernando Danilo
AU - Cabello-Verrugio, Claudio
N1 - Funding Information:
This study was supported by research grants from Association-Francaise Contre Les Myopathies AFM 16670 (CCV); Fondo Nacional de Desarrollo Científico y TecnológicoFONDECYT1120380, 1161646 (CCV), 1161288 (FS); Millennium Institute on Immunology and Immunotherapy P09-016-F (CCV, FS), UNAB DI-741-15/N (CCV, FS). VMM, JA, and JCR thank Conicyt for a PhD Scholarship. VMM. thanks CONICYT + PAI/“Concurso Nacional Tesis de Doctorado en la Empresa” 2014 (781413007). FGN, VMM, and IAD thank Fraunhofer Chile Research, Innova-Chile CORFO (FCR-CSB 09CEII-6991), Anillo Científico ACT1107, and RED CYTED 214RT0482 for their support The Centro Interdisciplinario de Neurociencia de Valparaíso (CINV) is a Millennium Institute supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo
Publisher Copyright:
© 2017 Márquez-Miranda et al.
PY - 2017/3/13
Y1 - 2017/3/13
N2 - 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.
AB - 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.
KW - Anti-atrophic peptide
KW - Carrier
KW - Muscle wasting
KW - Peptide delivery
UR - http://www.scopus.com/inward/record.url?scp=85015329806&partnerID=8YFLogxK
U2 - 10.2147/IJN.S125521
DO - 10.2147/IJN.S125521
M3 - Article
AN - SCOPUS:85015329806
SN - 1176-9114
VL - 12
SP - 1985
EP - 1999
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -