ArticlePloS one2016
Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways.Bioscience reports · 2026Review
- P38α deficiency alleviates myocardial ischemia/reperfusion injury by stabilizing c‑Myc to inhibit ferroptosis.Basic research in cardiology · 2026Article
- Diarylpropionitrile, a selective agonist of estrogen receptor β, protects the kidney against ischemia-reperfusion injury and enhances the repair of tubular epithelial cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Insights in ischemia/reperfusion injury and cardioprotection: neglected and emerging pathways and therapeutic targets for a personalized therapy.Basic research in cardiology · 2026Review
- Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury.BMC neuroscience · 2025Article
- The Anti-Parkinsonian A2A Receptor Antagonist Istradefylline (KW-6002) Attenuates Behavioral Abnormalities, Neuroinflammation, and Neurodegeneration in Cerebral Ischemia: An Adenosinergic Signaling Link Between Stroke and Parkinson's Disease.International journal of molecular sciences · 2025Article
- Review
- Estrogen Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.Cardiology research and practice · 2025Article
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- Prognostic factors of MINOCA and their possible mechanisms.Preventive medicine reports · 2024Review
- Review
- The combinatorial effect of age and biological sex on alloimmunity and transplantation outcome.Frontiers in transplantation · 2023Review
- The structure-function relationships and physiological roles of MnSOD mutants.Bioscience reports · 2022Review
- Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a.Cell communication and signaling : CCS · 2022Article
- Sex-Related Effects on Cardiac Development and Disease.Journal of cardiovascular development and disease · 2022Review
- Review
- Oestrogenic Regulation of Mitochondrial Dynamics.International journal of molecular sciences · 2022Review
- Estrogen signaling as a bridge between the nucleus and mitochondria in cardiovascular diseases.Frontiers in cell and developmental biology · 2022Review
- A Novel Role of Claudin-5 in Prevention of Mitochondrial Fission Against Ischemic/Hypoxic Stress in Cardiomyocytes.The Canadian journal of cardiology · 2021Article
- Progression of heart failure is attenuated by antioxidant therapy with N-acetylcysteine in myocardial infarcted female rats.Molecular biology reports · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β.
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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 Socratic graph.