ArticleCirculation research2017
ATF6 Decreases Myocardial Ischemia/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart.
Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers.
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Who cites it
195 citing papers in PubMed, 323 citations in OpenAlex.
- CD22Science China. Life sciences · 2026Article
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- A Potentially Protective Role for NRF2 in Endocannabinoid-Mediated Oxidative Stress in Human Coronary Artery Endothelial Cells.Cell biochemistry and biophysics · 2026Article
- Hepatic PDIA5 improves hyperglycaemia and insulin resistance through stabilisation of ATF6.Diabetologia · 2026Article
- Development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes.The Journal of physiology · 2026Article
- Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Glycitin Alleviates Myocardial Ischemia-reperfusion Injury By Suppressing Oxidative Stress and Apoptosis Through PI3K/Akt/NF-κB Pathway Modulation.Applied biochemistry and biotechnology · 2026Article
- Cardamonin activates AMPK/FOXO3a/Nrf-2 axis to ameliorate oxidative stress in hyperlipidemia induced cardiac injury in mice.Molecular biology reports · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Temporal Dynamics of Endothelium After Radiation Injury Reveal a Transient Pro-Angiogenic Capillary Subpopulation Associated with Skin Repair.International journal of molecular sciences · 2026Article
- Myocardial ischemia reperfusion in diabetes: mechanism of injury and its drug treatment.Diabetology & metabolic syndrome · 2026Review
- Repositioning of Alogliptin to Mitigate Secondary Injury Induced by Repetitive TBI: Potential Role of its Antioxidant and Anti- Inflammatory Effects.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Mucin 2 and unfolded protein response reshape the mucus barrier in inflammatory bowel disease (Review).Molecular medicine reports · 2026Review
- Human biliary atresia extrahepatic cholangiocyte organoids express increased ER and oxidative stress, altered drug metabolism and cell polarity changes.Frontiers in bioengineering and biotechnology · 2026Article
- Navigating Cellular Stress: Endoplasmic Reticulum Stress and the Unfolded Protein Response in the Molecular Pathogenesis of Preeclampsia.Cell biochemistry and biophysics · 2025Review
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
- A Redox-Active and Electroactive Hydrogel Enabled by an Integrated PEDOT@PMOF Nanofiller for Post-Infarct Myocardial Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- AI662270/GRP94 axis couples the unfolded protein response to mitochondrial dynamics during acute myocardial infarction.JCI insight · 2025Article
135 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleEndoplasmic reticulum (ER) stress causes the accumulation of misfolded proteins in the ER, activating the transcription factor, ATF6 (activating transcription factor 6 alpha), which induces ER stress response genes. Myocardial ischemia induces the ER stress response; however, neither the function of this response nor whether it is mediated by ATF6 is known.
objectiveHere, we examined the effects of blocking the ATF6-mediated ER stress response on ischemia/reperfusion (I/R) in cardiac myocytes and mouse hearts. METHODS AND
resultsKnockdown of ATF6 in cardiac myocytes subjected to I/R increased reactive oxygen species and necrotic cell death, both of which were mitigated by ATF6 overexpression. Under nonstressed conditions, wild-type and ATF6 knockout mouse hearts were similar. However, compared with wild-type, ATF6 knockout hearts showed increased damage and decreased function after I/R. Mechanistically, gene array analysis showed that ATF6, which is known to induce genes encoding ER proteins that augment ER protein folding, induced numerous oxidative stress response genes not previously known to be ATF6-inducible. Many of the proteins encoded by the ATF6-induced oxidative stress genes identified here reside outside the ER, including catalase, which is known to decrease damaging reactive oxygen species in the heart. Catalase was induced by the canonical ER stressor, tunicamycin, and by I/R in cardiac myocytes from wild-type but not in cardiac myocytes from ATF6 knockout mice. ER stress response elements were identified in the catalase gene and were shown to bind ATF6 in cardiac myocytes, which increased catalase promoter activity. Overexpression of catalase, in vivo, restored ATF6 knockout mouse heart function to wild-type levels in a mouse model of I/R, as did adeno-associated virus 9-mediated ATF6 overexpression.
conclusionsATF6 serves an important role as a previously unappreciated link between the ER stress and oxidative stress gene programs, supporting a novel mechanism by which ATF6 decreases myocardial I/R damage.
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