Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training

Sellamuthu S Gounder; Sankaranarayanan Kannan; Dinesh Devadoss; Corey J Miller; Kevin J Whitehead; Kevin S Whitehead; Shannon J Odelberg; Matthew A Firpo; Robert Paine III; John R Hoidal; E Dale Abel; Namakkal S Rajasekaran

doi:10.1371/journal.pone.0045697

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Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training

Journal article

Open access

Peer reviewed

Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training

Sellamuthu S Gounder, Sankaranarayanan Kannan, Dinesh Devadoss, Corey J Miller, Kevin J Whitehead, Kevin S Whitehead, Shannon J Odelberg, Matthew A Firpo, Robert Paine III, John R Hoidal, …

PloS one, Vol.7(9), pp.e45697-e45697

2012

DOI: 10.1371/journal.pone.0045697

PMCID: PMC3454427

PMID: 23029187

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Abstract

Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS) in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2) through antioxidant response cis-elements (AREs) and are impaired in the aging heart. Whereas acute exercise stress (AES) activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months), aging mouse (>23 months) hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES), but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day) for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

Oxidative Stress

Signal Transduction

Reactive Oxygen Species - metabolism

Electron Spin Resonance Spectroscopy

Oxidation-Reduction

Glutathione - metabolism

Mice, Inbred C57BL

Homeostasis

Male

Blotting, Western

Animals

Myocardium - metabolism

NF-E2-Related Factor 2 - metabolism

Transcription, Genetic

Mice

Fluorescent Dyes

Physical Conditioning, Animal

Details

Title: Subtitle: Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training
Creators: Sellamuthu S Gounder - Divisions of Cardiology and Pulmonary, Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA
Sankaranarayanan Kannan
Dinesh Devadoss
Corey J Miller - University of Utah
Kevin J Whitehead
Kevin S Whitehead
Shannon J Odelberg
Matthew A Firpo
Robert Paine III
John R Hoidal
E Dale Abel
Namakkal S Rajasekaran
Resource Type: Journal article
Publication Details: PloS one, Vol.7(9), pp.e45697-e45697
DOI: 10.1371/journal.pone.0045697
PMID: 23029187
PMCID: PMC3454427
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: 1R03AG042860-01 / NIA NIH HHS R01 HL118067 / NHLBI NIH HHS S10 RR027506 / NCRR NIH HHS R03 AG042860 / NIA NIH HHS
Language: English
Date published: 2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024529702771

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