Repositorio Institucional
Repositorio Institucional
CONICET Digital
  • Inicio
  • EXPLORAR
    • AUTORES
    • DISCIPLINAS
    • COMUNIDADES
  • Estadísticas
  • Novedades
    • Noticias
    • Boletines
  • Ayuda
    • General
    • Datos de investigación
  • Acerca de
    • CONICET Digital
    • Equipo
    • Red Federal
  • Contacto
JavaScript is disabled for your browser. Some features of this site may not work without it.
  • INFORMACIÓN GENERAL
  • RESUMEN
  • ESTADISTICAS
 
Artículo

Identification and characterization of sirtuin enzymes in cestodes and evaluation of sirtuin inhibitors as new cestocidal molecules

Vaca, Hugo RolandoIcon ; Celentano Stanic, Ana Maria Luisa Micaela; Toscanini, María AgustinaIcon ; Thomas Hausen, Alexander; Macchiaroli, NataliaIcon ; Cuestas, María LujánIcon ; Nusblat, Alejandro DavidIcon ; Sippl, Wolfgang; Elissondo, María CelinaIcon ; Jung, Manfred; Camicia, FedericoIcon ; Rosenzvit, Mara CeciliaIcon
Fecha de publicación: 04/2022
Editorial: Elsevier
Revista: International Journal for Parasitology
ISSN: 0020-7519
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Parasitología

Resumen

Anti-parasitic treatment of neglected tropical diseases caused by cestodes such as echinococcosis and cysticercosis relies on a small number of approved anthelmintic drugs. Furthermore, the treatment is usually prolonged and often partially effective and not well tolerated by some patients. Therefore, the identification of novel drug targets and their associated compounds is critical. In this study, we identified and characterised sirtuin enzymes in cestodes and evaluated the cestocidal potential of sirtuin inhibitors as new cestocidal molecules. Sirtuins are a highly conserved family of nicotinamide-adenine dinucleotide-lysine deacylases involved in multiple cellular functions. Here, we described the full repertoire of sirtuin-encoding genes in several cestode species. We identified six sirtuin-encoding genes that were classified into sirtuins Class I (SIRT1, SIRT2, and SIRT3), Class III (SIRT5), and Class IV (SIRT6 and SIRT7). In Echinococcus spp., sirtuin genes showed transcriptional expression throughout several developmental stages, sirtuin 2 (SIRT2) being the most expressed. To evaluate the potential of sirtuin inhibitors as new cestocidal molecules, we determined the in vitro effect of several Class I sirtuin inhibitors by motility assay. Of those, the selective SIRT2 inhibitor Mz25 showed a strong cestocidal activity in Mesocestoides vogae (syn. Mesocestoides corti) tetrathyridia at various concentrations. The Mz25 cestocidal activity was time- and dose-dependent with a half-maximal inhibitory concentration value significantly lower than that of albendazole. Additionally, Mz25 induced extensive damage in the general morphology with marked alterations in the tegument and ultrastructural features. By homology modelling, we found that cestode SIRT2s showed a high conservation of the canonical sirtuin structure as well as in the residues related to Mz25 binding. Interestingly, some non-conservative mutations were found on the selectivity pocket (an Mz25-induced structural rearrangement on the active site), which represent a promising lead for developing selective cestode SIRT2 inhibitors derived from Mz25. Nevertheless, the Mz25 molecular target in M. vogae is unknown and remains to be determined. This report provides the basis for further studies of sirtuins to understand their roles in cestode biology and to develop selective sirtuin inhibitors to treat these neglected tropical diseases.
Palabras clave: CESTODES , ECHINOCOCCUS , MESOCESTOIDES VOGAE , MZ25 , NEGLECTED TROPICAL DISEASES , SIRTUINS
Ver el registro completo
 
Archivos asociados
Thumbnail
 
Tamaño: 7.162Mb
Formato: PDF
.
Descargar
Licencia
info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/188955
URL: https://linkinghub.elsevier.com/retrieve/pii/S0020751922000157
DOI: http://dx.doi.org/10.1016/j.ijpara.2021.12.002
Colecciones
Articulos (IIPROSAM)
Articulos de INSTITUTO DE INVESTIGACIONES EN PRODUCCION, SANIDAD Y AMBIENTE
Articulos(IMPAM)
Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Articulos(NANOBIOTEC)
Articulos de INSTITUTO DE NANOBIOTECNOLOGIA
Articulos(OCA CIUDAD UNIVERSITARIA)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Vaca, Hugo Rolando; Celentano Stanic, Ana Maria Luisa Micaela; Toscanini, María Agustina; Thomas Hausen, Alexander; Macchiaroli, Natalia; et al.; Identification and characterization of sirtuin enzymes in cestodes and evaluation of sirtuin inhibitors as new cestocidal molecules; Elsevier; International Journal for Parasitology; 52; 5; 4-2022; 317-329
Compartir
Altmétricas
 

Enviar por e-mail
Separar cada destinatario (hasta 5) con punto y coma.
  • Facebook
  • X Conicet Digital
  • Instagram
  • YouTube
  • Sound Cloud
  • LinkedIn

Los contenidos del CONICET están licenciados bajo Creative Commons Reconocimiento 2.5 Argentina License

https://www.conicet.gov.ar/ - CONICET

Inicio

Explorar

  • Autores
  • Disciplinas
  • Comunidades

Estadísticas

Novedades

  • Noticias
  • Boletines

Ayuda

Acerca de

  • CONICET Digital
  • Equipo
  • Red Federal

Contacto

Godoy Cruz 2290 (C1425FQB) CABA – República Argentina – Tel: +5411 4899-5400 repositorio@conicet.gov.ar
TÉRMINOS Y CONDICIONES