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

Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: Possible implications in hypertension

Longo, Nadia AndreaIcon ; Corradi, Gerardo RaulIcon ; Lopez Verrilli, María AlejandraIcon ; Guil, María JuliaIcon ; Vatta, Marcelo SergioIcon ; Gironacci, Mariela MercedesIcon
Fecha de publicación: 02/2015
Editorial: Public Library of Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Médicas; Otras Ciencias Médicas

Resumen

Aberrations in the ubiquitin-proteasome system (UPS) are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR) and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86±15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2±8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92±22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7±0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasme activity. Proteasome activity was significantly reduced by 67±4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.
Palabras clave: TYROSINE HYDROXYLASE , PROTEASOME ACTIVITY , PC-12 CELLS , HYPERTENSION
Ver el registro completo
 
Archivos asociados
Thumbnail
 
Tamaño: 6.943Mb
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/11336/96265
URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116597
DOI: http://dx.doi.org/10.1371/journal.pone.0116597
Colecciones
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos(IQUIMEFA)
Articulos de INST.QUIMICA Y METABOLISMO DEL FARMACO (I)
Citación
Longo, Nadia Andrea; Corradi, Gerardo Raul; Lopez Verrilli, María Alejandra; Guil, María Julia; Vatta, Marcelo Sergio; et al.; Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: Possible implications in hypertension; Public Library of Science; Plos One; 10; 2; 2-2015; 1-18
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