ArticleAmerican journal of physiology. Cell physiology2019
Nuclear receptor subfamily 4 group A member 2 inhibits activation of ERK signaling and cell growth in response to β-adrenergic stimulation in adult rat cardiomyocytes.
Article in American journal of physiology. Cell physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Regulation of the murine preadipocytes differentiation by bitter taste receptor Tas2r108 and Tas2r126.Molecular and cellular biochemistry · 2026Article
- The Cavβ4 subunit of Cav1.2 channels antagonizes isoproterenol-induced hypertrophy in rat cardiac muscle cells by down-regulating miR-183-5p.Physiological reports · 2026Article
- NR4A2-driven metabolic reprogramming in the heart: from adaptive response to maladaptive remodeling.Physiological genomics · 2026Article
- Nuclear receptor subfamily 4 group a member 2 induces a Warburg-like effect and promotes phospholipids synthesis in the mouse heart.Physiological genomics · 2026Article
- The Nuclear Receptor Nurr1 Modulates the Expression and Activity of PPARγ in Human Pro-Inflammatory Macrophages.Scandinavian journal of immunology · 2025Article
- Rumen Epithelial Transcriptome Analysis Revealed the Regulatory Mechanism of Host Adaptation to Nitrogen Source Replacement Diet in Simmental Cattle.Food science & nutrition · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2021Review
- The molecular and epigenetic mechanisms of innate lymphoid cell (ILC) memory and its relevance for asthma.The Journal of experimental medicine · 2021Article
- Loss of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, and Insulin Resistance in Rats.Obesity (Silver Spring, Md.) · 2020Article
- Dietary Fat and Sugar Differentially Affect β-Adrenergic Stimulation of Cardiac ERK and AKT Pathways in C57BL/6 Male Mice Subjected to High-Calorie Feeding.The Journal of nutrition · 2020Article
- Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues.Cells · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 h) increase in NR4A2 levels that was accompanied by a transient (<24 h) increase in nuclear localization of the transcription factor. Adenovirus-mediated overexpression of NR4A2 to similar levels modulated the expression of genes linked to adrenoceptor signaling, calcium signaling, cell growth and proliferation and counteracted the increase in protein synthesis rate and cell surface area mediated by chronic isoproterenol stimulation. Consistent with those findings, NR4A2 overexpression also blocked the phosphorylative activation of growth-related kinases ERK1/2, Akt, and p70 S6 kinase. Prominent among the transcriptional changes induced by NR4A2 was the upregulation of the dual-specificity phosphatases DUSP2 and DUSP14, two known inhibitors of ERK1/2. Pretreatment of NR4A2-overexpressing cardiomyocytes with the DUSP inhibitor BCI [(
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