ArticleJournal of translational medicine2016
Abrogation of Nrf2 impairs antioxidant signaling and promotes atrial hypertrophy in response to high-intensity exercise stress.
Article in Journal of translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
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- The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors.Antioxidants (Basel, Switzerland) · 2022Review
- The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases.Cell & bioscience · 2022Review
- The ketone body β-hydroxybutyrate mitigates the senescence response of glomerular podocytes to diabetic insults.Kidney international · 2021Article
- Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox biology · 2020Review
- Dysregulation of nuclear factor erythroid 2-related factor 2 signaling and activation of fibrogenic pathways in hearts of high fat diet-fed rats.Molecular biology reports · 2020Article
- Impacts of exercise interventions on different diseases and organ functions in mice.Journal of sport and health science · 2020Review
- Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart.Nucleic acids research · 2019Article
- Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise.Antioxidants (Basel, Switzerland) · 2019Review
- Autophagy: A Lysosome-Dependent Process with Implications in Cellular Redox Homeostasis and Human Disease.Antioxidants & redox signaling · 2019Review
- Hydroxysafflor yellow A protects against angiotensin II‑induced hypertrophy.Molecular medicine reports · 2018Article
- An overview of the emerging interface between cardiac metabolism, redox biology and the circadian clock.Free radical biology & medicine · 2018Review
- Mechanical stretch induced transcriptomic profiles in cardiac myocytes.Scientific reports · 2018Article
- DL-3-n-Butylphthalide reduces atrial fibrillation susceptibility by inhibiting atrial structural remodeling in rats with heart failure.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Differential regulation of miRNA and mRNA expression in the myocardium of Nrf2 knockout mice.BMC genomics · 2017Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundAnomalies in myocardial structure involving myocyte growth, hypertrophy, differentiation, apoptosis, necrosis etc. affects its function and render cardiac tissue more vulnerable to the development of heart failure. Although oxidative stress has a well-established role in cardiac remodeling and dysfunction, the mechanisms linking redox state to atrial cardiomyocyte hypertrophic changes are poorly understood. Here, we investigated the role of nuclear erythroid-2 like factor-2 (Nrf2), a central transcriptional mediator, in redox signaling under high intensity exercise stress (HIES) in atria.
methodsAge and sex-matched wild-type (WT) and Nrf2(-/-) mice at >20 months of age were subjected to HIES for 6 weeks. Gene markers of hypertrophy and antioxidant enzymes were determined in the atria of WT and Nrf2(-/-) mice by real-time qPCR analyses. Detection and quantification of antioxidants, 4-hydroxy-nonenal (4-HNE), poly-ubiquitination and autophagy proteins in WT and Nrf2(-/-) mice were performed by immunofluorescence analysis. The level of oxidative stress was measured by microscopical examination of di-hydro-ethidium (DHE) fluorescence.
resultsUnder the sedentary state, Nrf2 abrogation resulted in a moderate down regulation of some of the atrial antioxidant gene expression (Gsr, Gclc, Gstα and Gstµ) despite having a normal redox state. In response to HIES, enlarged atrial myocytes along with significantly increased gene expression of cardiomyocyte hypertrophy markers (Anf, Bnf and β-Mhc) were observed in Nrf2(-/-) when compared to WT mice. Further, the transcript levels of Gclc, Gsr and Gstµ and protein levels of NQO1, catalase, GPX1 were profoundly downregulated along with GSH depletion and increased oxidative stress in Nrf2(-/-) mice when compared to its WT counterparts after HIES. Impaired antioxidant state and profound oxidative stress were associated with enhanced atrial expression of LC3 and ATG7 along with increased ubiquitination of ATG7 in Nrf2(-/-) mice subjected to HIES.
conclusionsLoss of Nrf2 describes an altered biochemical phenotype associated with dysregulation in genes related to redox state, ubiquitination and autophagy in HIES that result in atrial hypertrophy. Therefore, our findings direct that preserving Nrf2-related antioxidant function would be one of the effective strategies to safeguard atrial health.
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