The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of the EGF receptor/ERK pathway.
Free Radic Biol Med
; 32(6): 551-61, 2002 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-11958956
ABSTRACT
The nitrone spin trap PBN has been shown to protect neuronal cells from reactive oxygen species both in culture and in vivo. As an approach to understanding the molecular mechanisms by which PBN may function to protect cells, we examined whether PBN alters the cellular response to reactive oxygen species. H(2)O(2) stimulation of PC-12 cells results in weak activation of both the ERK and JNK signal transduction pathways. PBN pretreatment of PC-12 cells, followed by H(2)O(2) stimulation, results in strong and selective activation of the pro-survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN-pretreated cells results in only 30% of the increase in intracellular Ca(+2) as compared to untreated cells following H(2)O(2) stimulation. These data suggest a model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK pathway.
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Bases de datos:
MEDLINE
Asunto principal:
Depuradores de Radicales Libres
/
Proteínas Quinasas Activadas por Mitógenos
/
Proteínas Adaptadoras del Transporte Vesicular
/
Proteínas Adaptadoras Transductoras de Señales
/
Receptores ErbB
/
Peróxido de Hidrógeno
/
Óxidos de Nitrógeno
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos