ArticleThe Journal of clinical investigation2014
The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- The potential of TRPC channel-mediated autophagy in myocardial ischemia-reperfusion injury.Journal of cardiothoracic surgery · 2026Review
- From Serum to Genome: γ-Glutamyltransferase Gene Family Variants Shape Ischemic Stroke Risk via Sex-Specific Gene-Environment Interactions.Life (Basel, Switzerland) · 2026Article
- Detection of Noncovalent Protein-Ligand Complexes of D-DT Variants by MALDI-TOF Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Macrophage Migration Inhibitory Factor: the Next Adjunct to Reperfusion Therapy in Acute Myocardial Infarction?Cardiovascular drugs and therapy · 2025Article
- The multifaced role of the macrophage migration inhibitory factor family in organ fibrosis.American journal of physiology. Cell physiology · 2025Review
- An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Nature communications · 2025Article
- CAMKK2 is upregulated in primary human osteoarthritis and its inhibition protects against chondrocyte apoptosis.Osteoarthritis and cartilage · 2023Article
- SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice.Acta pharmacologica Sinica · 2023Article
- Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient miceActa pharmaceutica Sinica. B · 2023Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- The role of CD74 in cardiovascular disease.Frontiers in cardiovascular medicine · 2022Review
- MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model.The Journal of clinical investigation · 2021Article
- Brief report: Enhanced DRα1-mMOG-35-55 treatment of severe EAE in MIF-1-deficient male mice.Cellular immunology · 2021Article
- D-dopachrome tautomerase activates COX2/PGEJournal of neuroinflammation · 2021Article
- Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.Nature communications · 2020Article
- Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway.Frontiers in pharmacology · 2020Article
- Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair.Frontiers in immunology · 2020Review
- A selective small-molecule inhibitor of macrophage migration inhibitory factor-2 (MIF-2), a MIF cytokine superfamily member, inhibits MIF-2 biological activity.The Journal of biological chemistry · 2019Article
- Separating cytokine twins with a small molecule.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The cellular response to stress involves the recruitment and coordination of molecular signaling pathways that prevent cell death. D-dopachrome tautomerase (DDT) is an enzyme that lacks physiologic substrates in mammalian cells, but shares partial sequence and structural homology with macrophage migration inhibitory factor (MIF). Here, we observed that DDT is highly expressed in murine cardiomyocytes and secreted by the heart after ischemic stress. Antibody-dependent neutralization of secreted DDT exacerbated both ischemia-induced cardiac contractile dysfunction and necrosis. We generated cardiomyocyte-specific DDT knockout mice (Myh6-Cre Ddtfl/fl), which demonstrated normal baseline cardiac size and function, but had an impaired physiologic response to ischemia-reperfusion. Hearts from Myh6-Cre Ddtfl/fl mice exhibited more necrosis and LV contractile dysfunction than control hearts after coronary artery ligation and reperfusion. Furthermore, treatment with DDT protected isolated hearts against injury and contractile dysfunction after ischemia-reperfusion. The protective effect of DDT required activation of the metabolic stress enzyme AMP-activated protein kinase (AMPK), which was mediated by a CD74/CaMKK2-dependent mechanism. Together, our data indicate that cardiomyocyte secretion of DDT has important autocrine/paracrine effects during ischemia-reperfusion that protect the heart against injury.
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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.