ArticleThe Journal of biological chemistry2012
Induction of intracellular calcium concentration by environmental benzo(a)pyrene involves a β2-adrenergic receptor/adenylyl cyclase/Epac-1/inositol 1,4,5-trisphosphate pathway in endothelial cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 69 citations in OpenAlex.
- Inhibition of EPAC1 Prevents Neuronal Death Mediated by Diesel Exhaust Particles in Ferroptotic Cell Death Conditions.Antioxidants (Basel, Switzerland) · 2026Article
- The Effects of Air Pollution on Neurological Diseases: A Narrative Review on Causes and Mechanisms.Toxics · 2025Review
- Benzo[a]pyrene disrupts LH/hCG-dependent mouse Leydig cell steroidogenesis through receptor/Gαs protein targeting.Scientific reports · 2024Article
- Lung cancer associated with combustion particles and fine particulate matter (PMBiochemical pharmacology · 2023Review
- Article
- The β-Blocker Carvedilol Prevents Benzo(a)pyrene-Induced Lung Toxicity, Inflammation and Carcinogenesis.Cancers · 2023Article
- Effects of organic chemicals from diesel exhaust particles on adipocytes differentiated from human mesenchymal stem cells.Basic & clinical pharmacology & toxicology · 2023Article
- Potential role of polycyclic aromatic hydrocarbons in air pollution-induced non-malignant respiratory diseases.Respiratory research · 2020Review
- Selective Ah receptor modulators attenuate NPC1L1-mediated cholesterol uptake through repression of SREBP-2 transcriptional activity.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles.Environmental health : a global access science source · 2019Review
- Resolvin D2 elevates cAMP to increase intracellular [CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Molecular characterization of G-protein-coupled receptor (GPCR) and protein kinase A (PKA) cDNA inPeerJ · 2019Article
- Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling.International journal of molecular sciences · 2018Article
- Early Life Exposure to Low Levels of AHR Agonist PCB126 (3,3',4,4',5-Pentachlorobiphenyl) Reprograms Gene Expression in Adult Brain.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Catecholamines facilitate VEGF-dependent angiogenesis via β2-adrenoceptor-induced Epac1 and PKA activation.Oncotarget · 2017Article
- Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway.Scientific reports · 2017Article
- Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype.Scientific reports · 2017Article
- Comparative transcriptomic analyses to scrutinize the assumption that genotoxic PAHs exert effects via a common mode of action.Archives of toxicology · 2016Article
- Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms.Biomolecules · 2015Review
- Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water.Critical reviews in toxicology · 2015Review
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B(a)P) are widely distributed environmental contaminants, known as potent ligands of the aryl hydrocarbon receptor (AhR). These chemicals trigger an early and transient increase of intracellular calcium concentration ([Ca(2+)](i)), required for AhR-related effects of PAHs. The mechanisms involved in this calcium mobilization were investigated in the present study. We demonstrated that B(a)P-mediated [Ca(2+)](i) induction was prevented in endothelial HMEC-1 cells by counteracting β2-adrenoreceptor (β2ADR) activity using pharmacological antagonists, anti-β2ADR antibodies, or siRNA-mediated knockdown of β2ADR expression; by contrast, it was strongly potentiated by β2ADR overexpression in human kidney HEK293 cells. B(a)P was shown, moreover, to directly bind to β2ADR, as assessed by in vitro binding assays and molecular modeling. Pharmacological inhibition and/or siRNA-mediated silencing of various signaling actors acting downstream of β2ADR in a sequential manner, such as G protein, adenylyl cyclase, Epac-1 protein, and inositol 1,4,5-trisphosphate (IP(3))/IP(3) receptor, were next demonstrated to prevent B(a)P-induced calcium signal. Inhibition or knockdown of these signaling elements, as well as the use of chemical β-blockers, were finally shown to counteract B(a)P-mediated induction of cytochrome P-450 1B1, a prototypical AhR target gene. Taken together, our results show that B(a)P binds directly to β2ADR and consequently utilizes β2ADR machinery to mobilize [Ca(2+)](i), through activation of a G protein/adenylyl cyclase/cAMP/Epac-1/IP(3) pathway. This β2ADR-dependent signaling pathway activated by PAHs may likely be crucial for PAH-mediated up-regulation of AhR target genes, thus suggesting a contribution of β2ADR to the health-threatening effects of these environmental pollutants.
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