Your browser doesn't support javascript.
loading
Prion protein protects against zinc-mediated cytotoxicity by modifying intracellular exchangeable zinc and inducing metallothionein expression.
Rachidi, Walid; Chimienti, Fabrice; Aouffen, M'hammed; Senator, Abderrahmane; Guiraud, Pascale; Seve, Michel; Favier, Alain.
Afiliación
  • Rachidi W; INAC/SCIB/LAN, CEA de Grenoble, 17 rue des Martyrs, 38054 Grenoble, France. walid.rachidi@cea.fr
J Trace Elem Med Biol ; 23(3): 214-23, 2009.
Article en En | MEDLINE | ID: mdl-19486831
ABSTRACT
PrPC contains several octapeptide repeats sequences toward the N-terminus which have binding affinity for divalent metals such as copper, zinc, nickel and manganese. However, the link between PrPC expression and zinc metabolism remains elusive. Here we studied the relationship between PrPC and zinc ions intracellular homeostasis using a cell line expressing a doxycycline-inducible PrPC gene. No significant difference in 65Zn2+ uptake was observed in cells expressing PrPC when compared with control cells. However, PrPC-expressing cells were more resistant to zinc-induced toxicity, suggesting an adaptative mechanism induced by PrPC. Using zinquin-ethyl-ester, a specific fluorophore for vesicular free zinc, we observed a significant re-localization of intracellular exchangeable zinc in vesicles after PrPC expression. Finally, we demonstrated that PrPC expression induces metallothionein (MT) expression, a zinc-upregulated zinc-binding protein. Taken together, these results suggest that PrPC modifies the intracellular localization of zinc rather than the cellular content and induces MT upregulation. These findings are of major importance since zinc deregulation is implicated in several neurodegenerative disorders. It is postulated that in prion diseases the conversion of PrPC to PrPSc may deregulate zinc homeostasis mediated by metallothionein.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligoelementos / Zinc / Regulación de la Expresión Génica / Proteínas PrPC / Metalotioneína Límite: Animals Idioma: En Revista: J Trace Elem Med Biol Asunto de la revista: METABOLISMO / SAUDE AMBIENTAL Año: 2009 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligoelementos / Zinc / Regulación de la Expresión Génica / Proteínas PrPC / Metalotioneína Límite: Animals Idioma: En Revista: J Trace Elem Med Biol Asunto de la revista: METABOLISMO / SAUDE AMBIENTAL Año: 2009 Tipo del documento: Article País de afiliación: Francia