Role of JNK-1 regulation in the protection of contact-inhibited fibroblasts from oxidative stress.
Mol Cell Biochem
; 359(1-2): 105-13, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21822690
ABSTRACT
The molecular signaling events leading to protection from oxidative stress-induced apoptosis upon contact inhibition have not been fully investigated. Previous research has indicated a role for mitogen-activated protein kinases (MAPKs) in the regulation of contact inhibition, and these proteins have also been associated with cell cycle regulation and stress-induced apoptosis. The potential role of the MAPK JNK-1 in the stress-response of actively proliferating and contact-inhibited cells was investigated. Actively proliferating normal fibroblasts (BJ) and fibrosarcoma cells (HT-1080) were stressed with H2O2, and levels of activated JNK-1 and cleaved PARP were ascertained. Similarly, these results were compared with levels of activated JNK-1 and cleaved PARP detected in H2O2-stressed confluent fibrosarcoma or contact-inhibited fibroblast cells. Contact-inhibited fibroblasts were protected from apoptosis in comparison to subconfluent fibroblasts, concurrent with decreased JNK-1 activation. Increased culture density of fibrosarcoma cells was not protective against apoptosis, and these cells did not demonstrate density-dependent alterations in the JNK-1 stress response. This decreased activation of JNK-1 in stressed, contact-inhibited cells did not appear to be dependent upon increased expression of MKP-1; however, over-expression of MKP-1 was sufficient to result in a slight decrease in H2O2-stimulated PARP cleavage. Increasing the antioxidant capacity of fibroblasts through NAC-treatment not only lessened H2O2-stimulated JNK-1 activation, but also did not influence the expression of MKP-1. Taken together, these results suggest that regulation of negative regulation of JNK-1 upon contact inhibition is protective against apoptosis, and that this regulation is independent of MKP-1.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
/
Inhibición de Contacto
/
Proteína Quinasa 8 Activada por Mitógenos
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos