E4BP4 inhibits AngII-induced apoptosis in H9c2 cardiomyoblasts by activating the PI3K-Akt pathway and promoting calcium uptake.

Exp Cell Res

Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan. Electronic address:

Published: February 2018

The bZIP transcription factor E4BP4 is a survival factor that is known to be elevated in diseased heart and promote cell survival. In this study the role of E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to AngII to observe the cardio-protective effects of E4BP4 on hypertension related apoptosis. The results from TUNEL assays revealed that E4BP4 significantly attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of caspase-3 through the PI3K-Akt pathway. In addition, E4BP4 enhanced calcium reuptake into the sacroplasmic reticulum by down-regulating PP2A and by up-regulating the phosphorylation of PKA and PLB proteins. Our findings indicate that E4BP4 functions as a survival factor in cardiomyoblasts by inhibiting IGF-II transcription and by regulating calcium cycling.

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http://dx.doi.org/10.1016/j.yexcr.2018.01.012DOI Listing

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