ArticleMolecular pharmacology2012
Calcium channel blockers act through nuclear factor Y to control transcription of key cardiac genes.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook.International journal of molecular sciences · 2021Review
- Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular CaChannels (Austin, Tex.) · 2020Article
- Expression of recombinant classical swine fever virus E2 glycoprotein by endogenous Txnip promoter in stable transgenic CHO cells.Engineering in life sciences · 2020Article
- Verapamil extends lifespan inAging · 2020Article
- Thioredoxin-Interacting Protein (TXNIP) in Cerebrovascular and Neurodegenerative Diseases: Regulation and Implication.Molecular neurobiology · 2018Review
- The CCAAT box in the proximal SERCA2 gene promoter regulates basal and stress-induced transcription in cardiomyocytes.Molecular and cellular biochemistry · 2018Article
- Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP.Current opinion in endocrinology, diabetes, and obesity · 2018Review
- TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook.Current drug targets · 2017Review
- TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling.American journal of physiology. Heart and circulatory physiology · 2016Article
- Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling.Physiological genomics · 2015Article
- Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia.The Journal of biological chemistry · 2014Article
- Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell.Molecular endocrinology (Baltimore, Md.) · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
First-generation calcium channel blockers such as verapamil are a widely used class of antihypertensive drugs that block L-type calcium channels. We recently discovered that they also reduce cardiac expression of proapoptotic thioredoxin-interacting protein (TXNIP), suggesting that they may have unappreciated transcriptional effects. By use of TXNIP promoter deletion and mutation studies, we found that a CCAAT element was mediating verapamil-induced transcriptional repression and identified nuclear factor Y (NFY) to be the responsible transcription factor as assessed by overexpression/knockdown and luciferase and chromatin immunoprecipitation assays in cardiomyocytes and in vivo in diabetic mice receiving oral verapamil. We further discovered that increased NFY-DNA binding was associated with histone H4 deacetylation and transcriptional repression and mediated by inhibition of calcineurin signaling. It is noteworthy that the transcriptional control conferred by this newly identified verapamil-calcineurin-NFY signaling cascade was not limited to TXNIP, suggesting that it may modulate the expression of other NFY targets. Thus, verapamil induces a calcineurin-NFY signaling pathway that controls cardiac gene transcription and apoptosis and thereby may affect cardiac biology in previously unrecognized ways.
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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.