The Transcription Factor ATF4 Promotes Expression of Cell Stress Genes and Cardiomyocyte Death in a Cellular Model of Atrial Fibrillation

BioMed Research International
Johanna K FreundtPhilipp S Lange

Abstract

Cardiomyocyte remodelling in atrial fibrillation (AF) has been associated with both oxidative stress and endoplasmic reticulum (ER) stress and is accompanied by a complex transcriptional regulation. Here, we investigated the role the oxidative stress and ER stress responsive bZIP transcription factor ATF4 plays in atrial cardiomyocyte viability and AF induced gene expression. HL-1 cardiomyocytes were subjected to rapid field stimulation. Forced expression of ATF4 was achieved by adenoviral gene transfer. Using global gene expression analysis and chromatin immunoprecipitation, ATF4 dependent transcriptional regulation was studied, and tissue specimen of AF patients was analysed by immunohistochemistry. Oxidative stress and ER stress caused a significant reduction in cardiomyocyte viability and were associated with an induction of ATF4. Accordingly, ATF4 was also induced by rapid field stimulation mimicking AF. Forced expression of wild type ATF4 promoted cardiomyocyte death. ATF4 was demonstrated to bind to the promoters of several cell stress genes and to induce the expression of a number of ATF4 dependent stress responsive genes. Moreover, immunohistochemical analyses showed that ATF4 is expressed in the nuclei of cardiomyocyt...Continue Reading

References

Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·W C ClaycombN J Izzo
Feb 10, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Steven M WhiteWilliam C Claycomb
May 26, 2004·Cardiovascular Research·Bianca J J M BrundelRobert H Henning
Jul 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Krishna M Vattem, Ronald C Wek
Jan 29, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Takeshi HayashiPak H Chan
Jun 29, 2005·International Journal of Cardiology·Ruri OhkiKazuyuki Shimada
Jul 27, 2005·International Heart Journal·Nam-Ho KimJung Chaee Kang
Oct 26, 2005·Journal of Molecular and Cellular Cardiology·Guillaume LamiraultMarja Steenman
Feb 6, 2007·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Madison S SpachRoger C Barr
May 1, 2007·The International Journal of Biochemistry & Cell Biology·Kurosh Ameri, Adrian L Harris
Jul 3, 2007·Cell·Hamsa PuthalakathAndreas Strasser
Nov 10, 2007·Circulation Research·Christopher C Glembotski
Dec 7, 2007·Journal of Molecular and Cellular Cardiology·Christopher C Glembotski
May 7, 2008·The Journal of Experimental Medicine·Philipp S LangeRajiv R Ratan
Apr 1, 2008·Circulation. Arrhythmia and Electrophysiology·Stanley NattelDobromir Dobrev
Nov 13, 2010·Circulation Research·Jody GroenendykMarek Michalak
Aug 5, 2016·Nature Reviews. Cardiology·Stanley Nattel, Dobromir Dobrev
Sep 16, 2016·EMBO Reports·Karolina Pakos-ZebruckaAdrienne M Gorman
Nov 7, 2017·Nature Medicine·Kevin R KingRalph Weissleder
Feb 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Milan HanoZdena Sulová

❮ Previous
Next ❯

Citations

Dec 4, 2019·Cell Death & Disease·Myong-Ho JeongJong-Sun Kang
Apr 16, 2020·International Journal of Molecular Sciences·Arnab Ghosh, Natalia Shcherbik
Jul 4, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Fatemeh YarmohammadiGholamreza Karimi

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Immunoprecipitation
ChIP Seq
ChIP
Assay
gene array

Software Mentioned

Illumina GenomeStudio
DAVID
MS Excel
SPSS
BETA

Related Concepts

Related Feeds

Atrial Filbrillation

Atrial fibrillation refers to the abnormal heart rhythm characterized by rapid and irregular beating of the atria. Here is the latest research.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.