ArticleJournal of molecular and cellular cardiology2012
Protein disulfide isomerase-associated 6 is an ATF6-inducible ER stress response protein that protects cardiac myocytes from ischemia/reperfusion-mediated cell death.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence and In Vivo Tissue Ageing.Oxidative medicine and cellular longevity · 2015Pooled it
- Chemical induction and reversal of photoreceptor dystrophy in retinal organoids.Stem cell reports · 2026Article
- Multi-omics network reconstruction with collaborative graphical lasso.Bioinformatics (Oxford, England) · 2026Article
- Unfolded Protein Response in Glioblastoma: Mechanisms of Proteostasis, Tumor Adaptation, and Therapeutic Relevance.Neurochemical research · 2026Review
- Compartmental analysis of the pulmonary proteome reveals novel functions of the aryl hydrocarbon receptor.Respiratory research · 2026Article
- Myocardial Ischemia/Reperfusion Injury: Molecular Insights, Forensic Perspectives, and Therapeutic Horizons.Cells · 2025Review
- ATF6 enables pathogen infection in ticks by inducingProceedings of the National Academy of Sciences of the United States of America · 2025Article
- β-catenin as a key regulator of the cisplatin response in tumor cells.Clinical and experimental medicine · 2025Review
- Stress Management: How the Endoplasmic Reticulum Mitigates Protein Misfolding and Oxidative Stress by the Dual Role of Glutathione Peroxidase 8.Biomolecules · 2025Review
- Impact of ER stress and the unfolded protein response on Fabry disease.EBioMedicine · 2025Review
- Exploring Endocannabinoid System: Unveiling New Roles in Modulating ER Stress.Antioxidants (Basel, Switzerland) · 2024Review
- Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells.BMB reports · 2024Article
- Supervised discovery of interpretable gene programs from single-cell data.Nature biotechnology · 2024Article
- Effects of Natural Products through Inhibiting Endoplasmic Reticulum Stress on Attenuation of Idiopathic Pulmonary Fibrosis.Drug design, development and therapy · 2024Review
- Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.Science advances · 2023Review
- Vaccinia virus induces endoplasmic reticulum stress and activates unfolded protein responses through the ATF6α transcription factor.Virology journal · 2023Article
- Imbalanced unfolded protein response signaling contributes to 1-deoxysphingolipid retinal toxicity.Nature communications · 2023Article
- α-Gal A missense variants associated with Fabry disease can lead to ER stress and induction of the unfolded protein response.Molecular genetics and metabolism reports · 2022Article
- Endoplasmic Reticulum Stress Underlies Nanosilver-Induced Neurotoxicity in Immature Rat Brain.International journal of molecular sciences · 2022Article
- Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review).Experimental and therapeutic medicine · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Proper folding of secreted and transmembrane proteins made in the rough endoplasmic reticulum (ER) requires oxygen for disulfide bond formation. Accordingly, ischemia can impair ER protein folding and initiate the ER stress response, which we previously showed is activated in the ischemic heart and in culture cardiac myocytes subjected to simulated ischemia. ER stress and ischemia activate the transcription factor, activating transcription factor 6 (ATF6), which induces numerous genes, many of which have not been identified, or examined in the heart. Using an ATF6 transgenic mouse model, we previously showed that ATF6 protected the heart from ischemic damage; however, the mechanism of this protection remains to be determined. In this study, we showed that, in the mouse heart, and in cultured cardiac myocytes, ATF6 induced the protein disulfide isomerase associated 6 (PDIA6) gene, which encodes an ER enzyme that catalyzes protein disulfide bond formation. Moreover, in cultured cardiac myocytes, ER stress-mediated PDIA6 promoter activation was ATF6-dependent, and required an ER stress response element (ERSE) and a nearby CCAAT box element. Electromobility shift assays and chromatin immunoprecipitation showed that ATF6 bound to the ERSE in the PDIA6 promoter, in vitro, and in the mouse heart, in vivo. Gain- and loss-of-function studies showed that PDIA6 protected cardiac myocytes against simulated ischemia/reperfusion-induced death in a manner that was dependent on the catalytic activity of PDIA6. Thus, by facilitating disulfide bond formation, and enhanced ER protein folding, PDIA6 may contribute to the protective effects of ATF6 in the ischemic mouse heart.
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