ArticleMolecules (Basel, Switzerland)2015
KMUP-1 Attenuates Endothelin-1-Induced Cardiomyocyte Hypertrophy through Activation of Heme Oxygenase-1 and Suppression of the Akt/GSK-3β, Calcineurin/NFATc4 and RhoA/ROCK Pathways.
Article in Molecules (Basel, Switzerland), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
12 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Antiatherogenic and Cardioprotective Effects of a Xanthine Derivative KMUP-1 in ApoE Knockout Mice.Cardiovascular therapeutics · 2025Article
- Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.Cell cycle (Georgetown, Tex.) · 2023Review
- Endothelin A receptor antagonist attenuated renal iron accumulation in iron overload heme oxygenase-1 knockout mice.Canadian journal of physiology and pharmacology · 2022Article
- [8]-Gingerol exerts anti-myocardial ischemic effects in rats via modulation of the MAPK signaling pathway and L-type CaPharmacology research & perspectives · 2021Article
- Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53.Journal of personalized medicine · 2021Article
- The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor.Oxidative medicine and cellular longevity · 2020Review
- KMUP-1 Ameliorates Ischemia-Induced Cardiomyocyte Apoptosis through the NO⁻cGMP⁻MAPK Signaling Pathways.Molecules (Basel, Switzerland) · 2019Article
- The Effects of Dracocephalum Heterophyllum Benth Flavonoid on Hypertrophic Cardiomyocytes Induced by Angiotensin II in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in cardiomyoblasts are counteracted by beta estradiol: in vitro and in vivo studies.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- 5-HT induces PPAR γ reduction and proliferation of pulmonary artery smooth muscle cells via modulating GSK-3β/β-catenin pathway.Oncotarget · 2017Article
- Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice.International journal of molecular sciences · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner. In addition, KMUP-1 prevented ET-1-induced intracellular reactive oxygen species generation determined by the DCFH-DA assay in cardiomyocytes. KMUP-1 also attenuated phosphorylation of ERK1/2 and Akt/GSK-3β, and activation of calcineurin/NFATc4 and RhoA/ROCK pathways induced by ET-1. Furthermore, we found that the expression of heme oxygenase-1 (HO-1), a stress-response enzyme implicated in cardio-protection, was up-regulated by KMUP-1. Finally, KMUP-1 attenuated ET-1-stimulated activator protein-1 DNA binding activity. In conclusion, KMUP-1 attenuates cardiomyocyte hypertrophy induced by ET-1 through inhibiting ERK1/2, calcineurin/NFATc4 and RhoA/ROCK pathways, with associated cardioprotective effects via HO-1 activation. Therefore, KMUP-1 may have a role in pharmacological therapy of cardiac hypertrophy.
Indexed as
Identifiers
What OpenQuestion holds
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.