Overexpression of CREB protein protects from tunicamycin-induced apoptosis in various rat cell types.
Apoptosis
; 19(7): 1080-98, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24722832
ABSTRACT
Endoplasmic reticulum (ER) stress plays an essential role in unfolded protein response induced apoptosis contributing to several pathological conditions. Glycogen synthase kinase-3ß (GSK-3ß) plays a central role in several apoptotic signaling, including ER stress, as the active form of GSK-3ß induces apoptosis. The phosphorylation of cAMP responsive element (CRE) binding protein (CREB) Ser-133 (S133) residue is the end-point of various signaling pathways, like growth factor signaling, while the Ser-129 (S129) residue is phosphorylated by GSK-3ß. The significance of the ubiquitously expressed transcription factor CREB is demonstrated in prolonged, tunicamycin (TM)-induced ER stress in this study. In the experiments wild-type (wt) CREB, S129Ala, S133Ala or S129Ala-S133Ala mutant CREB expressing PC12 rat pheochromocytoma cell lines showed increased survival under TM-evoked prolonged ER stress compared to wtPC12 cells. After TM treatment ER stress was activated in all PC12 cell types. Lithium and SB-216763, the selective, well-known inhibitors of GSK-3ß, decreased TM-induced apoptosis and promoted cell survival. The proapoptotic BH3-only Bcl-2 family member Bcl-2-interacting mediator of cell death (Bim) level was decreased in the different CREB overexpressing PC12 cells as a result of TM treatment. CREB overexpression also inhibited the sequestration of Bim protein from tubulin molecules, as it was demonstrated in wtPC12 cells. Transient expression of wtCREB diminished TM-induced apoptosis in wtPC12, Rat-1 and primary rat vascular smooth muscle cells. These findings demonstrate a novel role of CREB in different cell types as a potent protector against ER stress.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tunicamicina
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
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Apoptosis
/
Estrés del Retículo Endoplásmico
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Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Apoptosis
Año:
2014
Tipo del documento:
Article
País de afiliación:
Hungria