Overexpression of CREB protein protects from tunicamycin-induced apoptosis in various rat cell types

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Item Type:	Article
Title:	Overexpression of CREB protein protects from tunicamycin-induced apoptosis in various rat cell types
Creators Name:	Balogh, A., Németh, M., Koloszár, I., Markó, L., Przybyl, L., Jinno, K., Szigeti, C., Heffer, M., Gebhardt, M., Szeberényi, J., Müller, D.N., Sétáló, G. and Pap, M.
Abstract:	Endoplasmic reticulum (ER) stress plays an essential role in unfolded protein response induced apoptosis contributing to several pathological conditions. Glycogen synthase kinase-3β (GSK-3β) plays a central role in several apoptotic signaling, including ER stress, as the active form of GSK-3β 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-3β. 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-3β, 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.
Keywords:	Apoptosis, ER Stress, Unfolded Protein Response, Tunicamycin, CREB, PC12 Cells, Animals, Rats
Source:	Apoptosis
ISSN:	1360-8185
Publisher:	Springer
Volume:	19
Number:	7
Page Range:	1080-1098
Date:	1 July 2014
Official Publication:	https://doi.org/10.1007/s10495-014-0986-z
PubMed:	View item in PubMed

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