Arsenic trioxide and angiotensin II have inhibitory effects on HERG protein expression: Evidence for the role of PML SUMOylation

Oncotarget
Yu LiuBaofeng Yang

Abstract

The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II. Conversely, knockdown of RNF4 led to a remarkable increase in PML SUMOylation and the function of PML-NBs, further promoting ATO- or Ang II-induced HERG protein downregulation. Mechanistically, an increase in PML SUMOylation by ATO or Ang II dramatically enhanced the formation of PML and Pin1 complexes in PML-NBs, leading to the upregulation of TGF-β1 protein, eventually inhibiting HERG expression through activation of protein kinase A. The present work uncovered a novel molecular mechanism underlying HERG protein ex...Continue Reading

References

May 9, 1998·The Journal of Biological Chemistry·L WangK Sharma
Dec 22, 1999·Histochemistry and Cell Biology·C A May
May 30, 2001·Progress in Biophysics and Molecular Biology·D Fedida, J C Hesketh
Dec 6, 2005·Developmental Cell·Michael R Kuehn
Dec 6, 2005·Developmental Cell·Karim NacerddineAnne Dejean
Mar 24, 2006·Nature·Michael C Sanguinetti, Martin Tristani-Firouzi
Jan 12, 2008·The Journal of Clinical Investigation·Zhong-Jian ShenJames S Malter
Apr 15, 2008·Nature Cell Biology·Valérie Lallemand-BreitenbachHugues de Thé
Apr 15, 2008·Nature Cell Biology·Michael H TathamRonald T Hay
Feb 24, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jian ChenThomas V McDonald
Nov 17, 2010·Pharmacological Reviews·Prince KannankerilDawood Darbar
Jun 5, 2012·Genes & Development·Yaron GalantyStephen P Jackson
Dec 21, 2013·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Liliang ShuJing Xu
Mar 19, 2014·The Journal of Cell Biology·Umut SahinValérie Lallemand-Breitenbach
Aug 21, 2014·The Journal of Pathology·Umut SahinHugues de Thé
Nov 15, 2014·Basic & Clinical Pharmacology & Toxicology·Xin ZhaoBao-Xin Li
Jul 22, 2015·Nature Reviews. Cardiology·Gerrit Frommeyer, Lars Eckardt
Feb 2, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yu LiuWen-Feng Chu

❮ Previous
Next ❯

Citations

May 28, 2019·Current Treatment Options in Oncology·Sanjay Chandrasekhar, Michael G Fradley

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
Co-immunoprecipitation
mechanical dissociation
transfections

Software Mentioned

Pro
Prism
Odyssey
Image
GraphPad

Related Concepts

Related Feeds

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.

Cardiovascular Homeostasis

Cardiovascular regulation and homeostasis is important in maintaining health and dysfunction may lead to cardiovascular diseases. Nitric oxide and vascular endothelium are one of many molecules involved in the homeostatic mechanism. Here is the latest research on cardiovascular homeostasis.

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.

Cardiotoxicity

Cardiotoxicity refers to the muscle damage or dysfunction of heart electrophysiology caused by drug intake or due to disease complications. It is a well-known side effect of several cytotoxic drugs, especially of the anthracyclines and can lead to long term morbidity. Here is the latest research.

Related Papers

Molecular Therapy : the Journal of the American Society of Gene Therapy
Yu LiuWenfeng Chu
Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Wen-Xiao XuJinglong Yan
European Journal of Pharmacology
Hisashi Nogawa, Tomoyuki Kawai
Nihon rinsho. Japanese journal of clinical medicine
Hiroshi Kishida
© 2022 Meta ULC. All rights reserved