ArticleAntioxidants & redox signaling2011
Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice.
Article in Antioxidants & redox signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 141 citations in OpenAlex.
- Molecular mechanisms of cardioprotection: biomarkers, signaling pathways, and emerging molecular signatures in cardiovascular disease.Molecular biology reports · 2026Review
- Targeted activation of Nrf2 via sulforaphane-loaded exosomes attenuated azoospermic condition in the rat model.Scientific reports · 2026Article
- Reductive stress: The key pathway in metabolic disorders induced by overnutrition.Journal of advanced research · 2025Review
- Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12.Cell reports · 2025Article
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- Importance of systemic redox homeostasis biomarkers and transcription factors in patients undergoing open-heart surgery with cardiopulmonary bypass.Surgery today · 2025Article
- Impaired Renal Function Due to Reductive Stress Is Associated with Excessive Consumption ofAntioxidants (Basel, Switzerland) · 2025Article
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Intracellular dehydrogenation catalysis leads to reductive stress and immunosuppression.Nature nanotechnology · 2025Article
- Article
- Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism.iScience · 2024Article
- Cardiovascular aging: spotlight on mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Review
- Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes.Antioxidants (Basel, Switzerland) · 2023Article
- The bridge between cell survival and cell death: reactive oxygen species-mediated cellular stress.EXCLI journal · 2023Review
- More than Just Antioxidants: Redox-Active Components and Mechanisms Shaping Redox Signalling Network.Antioxidants (Basel, Switzerland) · 2022Review
- Transgenic Expression of Nrf2 Induces a Pro-Reductive Stress and Adaptive Cardiac Remodeling in the Mouse.Genes · 2022Article
- Review
- The deubiquitinase USP15 modulates cellular redox and is a therapeutic target in acute myeloid leukemia.Leukemia · 2022Article
- Article
- Relationship between oxidative stress and nuclear factor-erythroid-2-related factor 2 signaling in diabetic cardiomyopathy (Review).Experimental and therapeutic medicine · 2021Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Inheritable missense mutations in small molecular weight heat-shock proteins (HSP) with chaperone-like properties promote self-oligomerization, protein aggregation, and pathologic states such as hypertrophic cardiomyopathy in humans. We recently described that human mutant αB-crystallin (hR120GCryAB) overexpression that caused protein aggregation cardiomyopathy (PAC) was genetically linked to dysregulation of the antioxidant system and reductive stress (RS) in mice. However, the molecular mechanism that induces RS remains only partially understood. Here we define a critical role for the regulatory nuclear erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein (Keap1) pathway--the master transcriptional controller of antioxidants, in the pathogenesis of PAC and RS. In myopathic mice, increased reactive oxygen species signaling during compensatory hypertrophy (i.e., 3 months) was associated with upregulation of key antioxidants in a manner consistent with Nrf2/antioxidant response element (ARE)-dependent transactivation. In transcription factor assays, we further demonstrate increased binding of Nrf2 to ARE during the development of cardiomyopathy. Of interest, we show that the negative regulator Keap1 was predominantly sequestrated in protein aggregates (at 6 months), suggesting that sustained nuclear translocation of activated Nrf2 may be a contributing mechanism for RS. Our findings implicate a novel pathway for therapeutic targeting and abrogating RS linked to experimental cardiomyopathy in humans. Antioxid.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.