ArticleJournal of cellular physiology2012
High glucose-induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling.
Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 65 citations in OpenAlex.
- Integrating network toxicology, machine learning, and molecular dynamics simulations to reveal tanshinone iia's dual mechanisms in TNBC and doxorubicin-induced cardiotoxicity.Scientific reports · 2026Article
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- Analysis of alcohol-metabolizing enzymes genetic variants and RAR/RXR expression in patients diagnosed with fetal alcohol syndrome: a case-control study.BMC genomics · 2024Article
- Retinoic Acid Receptor Is a Novel Therapeutic Target for Postoperative Cognitive Dysfunction.Pharmaceutics · 2023Article
- Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism.Nature cell biology · 2023Article
- Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2021Review
- Electronegative low-density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade.Journal of diabetes investigation · 2020Article
- Exploring the Antihyperglycemic Chemical Composition and Mechanisms of Tea Using Molecular Docking.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy.Biomolecules · 2019Article
- Zeaxanthin Isolated fromMarine drugs · 2019Article
- Retinol but not retinoic acid can enhance the glutathione level, in a manner similar to β-carotene, in a murine cultured macrophage cell line.Food science & nutrition · 2018Article
- Integrated metabolic models for xenobiotic induced mitochondrial toxicity in skeletal muscle.Redox biology · 2018Article
- Loss of myocardial retinoic acid receptor α induces diastolic dysfunction by promoting intracellular oxidative stress and calcium mishandling in adult mice.Journal of molecular and cellular cardiology · 2016Article
- Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved.Journal of lipid research · 2016Article
- Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice.Hepatology (Baltimore, Md.) · 2016Article
- Retinoid X receptor α overexpression alleviates mitochondrial dysfunction-induced insulin resistance through transcriptional regulation of insulin receptor substrate 1.Molecules and cells · 2015Article
- Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
- Mechanisms for the adverse effects of late gestational increases in maternal cortisol on the heart revealed by transcriptomic analyses of the fetal septum.Physiological genomics · 2014Article
- Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling.Journal of clinical medicine · 2014Review
- The PI3K/AKT Pathway and FOXO3a Transcription Factor Mediate High Glucose-Induced Apoptosis in Neonatal Rat Ventricular Myocytes.Iranian Red Crescent medical journal · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The biological actions of retinoids are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have recently reported that decreased expression of RARα and RXRα has an important role in high glucose (HG)-induced cardiomyocyte apoptosis. However, the regulatory mechanisms of HG effects on RARα and RXRα remain unclear. Using neonatal cardiomyocytes, we found that ligand-induced promoter activity of RAR and RXR was significantly suppressed by HG. HG promoted protein destabilization and serine-phosphorylation of RARα and RXRα. Proteasome inhibitor MG132 blocked the inhibitory effect of HG on RARα and RXRα. Inhibition of intracellular reactive oxidative species (ROS) abolished the HG effect. In contrast, H(2)O(2) stimulation suppressed the expression and ligand-induced promoter activity of RARα and RXRα. HG promoted phosphorylation of ERK1/2, JNK and p38 MAP kinases, which was abrogated by an ROS inhibitor. Inhibition of JNK, but not ERK and p38 activity, reversed HG effects on RARα and RXRα. Activation of JNK by over expressing MKK7 and MEKK1, resulted in significant downregulation of RARα and RXRα. Ligand-induced promoter activity of RARα and RXRα was also suppressed by overexpression of MEKK1. HG-induced cardiomyocyte apoptosis was potentiated by activation of JNK, and prevented by all-trans retinoic acid and inhibition of JNK. Silencing the expression of RARα and RXRα activated the JNK pathway. In conclusion, HG-induced oxidative stress and activation of the JNK pathway negatively regulated expression/activation of RAR and RXR. The impaired RAR/RXR signaling and oxidative stress/JNK pathway forms a vicious circle, which significantly contributes to hyperglycemia induced cardiomyocyte apoptosis.
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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.