ArticleInternational journal of cardiology2014
15-deoxy-Δ¹²,¹⁴-PGJ₂ promotes inflammation and apoptosis in cardiomyocytes via the DP2/MAPK/TNFα axis.
Article in International journal of cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 35 citations in OpenAlex.
- Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP.Scientific reports · 2019Trial
- SGLT2 Inhibitor Might Prevent Atrial Fibrillation Related to Metabolic Syndrome via TNF-α Signaling Pathway: A Bioinformatic Study.Journal of arrhythmia · 2025Article
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- CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling.Journal of neuroinflammation · 2025Article
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- Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation.International journal of molecular sciences · 2021Article
- Increased prostaglandin-D2 in male STAT3-deficient hearts shifts cardiac progenitor cells from endothelial to white adipocyte differentiation.PLoS biology · 2020Article
- Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis.Biomolecules · 2020Review
- DP1 receptor signaling prevents the onset of intrinsic apoptosis in eosinophils and functions as a transcriptional modulator.Journal of leukocyte biology · 2018Article
- CRTH2 promotes endoplasmic reticulum stress-induced cardiomyocyte apoptosis through m-calpain.EMBO molecular medicine · 2018Article
- Saxagliptin but Not Sitagliptin Inhibits CaMKII and PKC via DPP9 Inhibition in Cardiomyocytes.Frontiers in physiology · 2018Article
- Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis.Journal of the American Heart Association · 2017Article
- The therapeutic potential of CRTH2/DP2 beyond allergy and asthma.Prostaglandins & other lipid mediators · 2017Review
- Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin DThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Serum brain-derived neurotrophic factor and risk of atrial fibrillation.American heart journal · 2017Article
- Activation of the MAPK/Akt/Nrf2-Egr1/HO-1-GCLc axis protects MG-63 osteosarcoma cells against 15d-PGJ2-mediated cell death.Biochemical pharmacology · 2016Article
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10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundProstaglandins (PGs), lipid autacoids derived from arachidonic acid, play a pivotal role during inflammation. PGD₂ synthase is abundantly expressed in heart tissue and PGD₂ has recently been found to induce cardiomyocyte apoptosis. PGD₂ is an unstable prostanoid metabolite; therefore the objective of the present study was to elucidate whether its final dehydration product, 15-deoxy-Δ¹²,¹⁴-PGJ₂ (15d-PGJ₂, present at high levels in ischemic myocardium) might cause cardiomyocyte damage. METHODS AND
resultsUsing specific (ant)agonists we show that 15d-PGJ₂ induced formation of intracellular reactive oxygen species (ROS) and phosphorylation of p38 and p42/44 MAPKs via the PGD2 receptor DP2 (but not DP1 or PPARγ) in the murine atrial cardiomyocyte HL-1 cell line. Activation of the DP2-ROS-MAPK axis by 15d-PGJ₂ enhanced transcription and translation of TNFα and induced apoptosis in HL-1 cardiomyocytes. Silencing of TNFα significantly attenuated the extrinsic (caspase-8) and intrinsic apoptotic pathways (bax and caspase-9), caspase-3 activation and downstream PARP cleavage and γH2AX activation. The apoptotic machinery was unaffected by intracellular calcium, transcription factor NF-κB and its downstream target p53. Of note, 9,10-dihydro-15d-PGJ₂ (lacking the electrophilic carbon atom in the cyclopentenone ring) did not activate cellular responses. Selected experiments performed in primary murine cardiomyocytes confirmed data obtained in HL-1 cells namely that the intrinsic and extrinsic apoptotic cascades are activated via DP2/MAPK/TNFα signaling.
conclusionsWe conclude that the reactive α,β-unsaturated carbonyl group of 15d-PGJ₂ is responsible for the pronounced upregulation of TNFα promoting cardiomyocyte apoptosis. We propose that inhibition of DP2 receptors could provide a possibility to modulate 15d-PGJ₂-induced myocardial injury.
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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.