Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion.

Authors

Ke Wang, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow
Jie Zhang, Department of Physiology, Shanxi Medical University
Xiaoliang Wang, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Xin Liu, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow
Lin Zuo, Department of Physiology, Shanxi Medical UniversityFollow
Kehua Bai, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University
Jianyu Shang, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow
Lu Ma, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow
Teng Liu, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University
Li Wang, Department of Physiology, Shanxi Medical University
Wen Wang, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow
Xin-Liang Ma, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Huirong Liu, Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical UniversityFollow

Document Type

Article

Publication Date

10-1-2013

Comments

This article has been peer reviewed. It was published in: Rejuvenation Research.

Volume 16, Issue 5, 1 October 2013, Pages 377-385.

The published version is available at DOI: 10.1089/rej.2013.1437

Copyright © 2013, Mary Ann Liebert, Inc.

Abstract

The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young and aging rats. Increased nitrogen oxide (NOx) but decreased nitric oxide (NO) bioavailability (decreased phosphorylated vasodilator-stimulated phosphoprotein) was observed in aging hearts. Peroxynitrite (ONOO⁻) was increased in aging hearts and was further amplified after MI/R. TrxR nitration in young and aging hearts was detected by immunoprecipitation (anti-nitrotyrosine) followed by immunoblotting (anti-TrxR). Compared with young hearts, TrxR nitration was increased in the aging hearts, and this was further intensified after MI/R. The ONOO⁻ decomposition catalyst (FeTMPyp) reduced TrxR nitration and increased TrxR and Trx activity. More importantly, FeTMPyp attenuated the MI/R injury in aging hearts as evidenced by decreased caspase-3 and malondialdehyde (MDA) concentration and increased cardiac function. Increased ONOO⁻ nitrated TrxR in the aging heart as a post-translational modification, which may be related to the enhanced MI/R injury of aging rats. Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart.

Recommended Citation

Wang, Ke; Zhang, Jie; Wang, Xiaoliang; Liu, Xin; Zuo, Lin; Bai, Kehua; Shang, Jianyu; Ma, Lu; Liu, Teng; Wang, Li; Wang, Wen; Ma, Xin-Liang; and Liu, Huirong, "Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion." (2013). Department of Emergency Medicine Faculty Papers. Paper 36.
https://jdc.jefferson.edu/emfp/36

PubMed ID

23802942