The Role of SUMO-1 in Cardiac Oxidative Stress and Hypertrophy

Overview

Journal Antioxid Redox Signal

Specialty Endocrinology

Date 2014 Jun 4

PMID 24893265

Citations 43

Authors

Ahyoung Lee

Dongtak Jeong

Shinichi Mitsuyama

Jae Gyun Oh

Lifan Liang

Yoshiyuki Ikeda

Junichi Sadoshima

Roger J Hajjar

Changwon Kho

Affiliations

Soon will be listed here.

Abstract

Aims: Small ubiquitin-like modifier type 1 (SUMO-1) has been shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure. In cardiac hypertrophy, the role of SUMO-1 has not been defined and our study's goals were to examine the effects of modulating SUMO-1 on the hypertrophic response both in vitro and in vivo and to examine whether oxidative stress (during cardiac hypertrophy) is abrogated by SUMO-1 gene transfer.

Results: In mice undergoing transverse aortic constriction (TAC), SUMO-1 levels increased slightly during the compensated stage of hypertrophy and then dropped sharply during the transition to heart failure. In isolated cardiomyocytes, SUMO-1 gene transfer inhibited the hypertrophic response in the presence of phenylephrine. Adeno-associated vector type 9 (AAV9) gene transfer of SUMO-1 prevented the heart from undergoing hypertrophy after TAC and prevented the development of left ventricular dysfunction. Furthermore, SUMO-1 gene transfer blocked the negative effects of H2O2 on SERCA2a activity in cardiac myocytes, while in vivo indices of oxidative stress were decreased by SUMO-1 in cardiac hypertrophy and heart failure.

Innovation And Conclusion: The results of this study indicate that post-translational modifications of SERCA2a caused by the toxic environment of the hypertrophied and failing myocardium can be prevented by SUMO-1. Antioxid. Redox Signal. 21, 1986-2001.

Citing Articles

Epigenetics in Heart Failure.

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