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

Bih Cheng Chen, Marthandam Asokan Shibu, Chia Hua Kuo, Chia Yao Shen, Shu Nu Chang-Lee, Chao Hung Lai, Ray Jade Chen, Chun Hsu Yao, Vijaya Padma Viswanadha, Jian Shen Liu, Wei Kung Chen, Chih Yang Huang

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalExperimental Cell Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Keywords

  • Angiotensin II
  • Calcium channels
  • E4 promoter-binding protein 4
  • Hypertrophy

ASJC Scopus subject areas

  • Cell Biology

Cite this

Chen, B. C., Shibu, M. A., Kuo, C. H., Shen, C. Y., Chang-Lee, S. N., Lai, C. H., Chen, R. J., Yao, C. H., Viswanadha, V. P., Liu, J. S., Chen, W. K., & Huang, C. Y. (Accepted/In press). E4BP4 inhibits AngII-induced apoptosis in H9c2 cardiomyoblasts by activating the PI3K-Akt pathway and promoting calcium uptake. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2018.01.012