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Minding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity
Open accessAbstract
Chronic low-level polychlorinated biphenyl (PCB) exposures remain a significant public health concern since results from epidemiological studies indicate that PCB burden is associated with immune system dysfunction, cardiovascular disease, and impairment of the developing nervous system. Of these various adverse health effects, developmental neurotoxicity has emerged as a particularly vulnerable endpoint in PCB toxicity. Arguably the most pervasive biological effects of PCBs could be mediated by their ability to alter the spatial and temporal fidelity of Ca2+ signals through one or more receptor-mediated processes. This review will focus on our current knowledge of the structure and function of ryanodine receptors (RyRs) in muscle and nerve cells and how PCBs and related non-coplanar structures alter these functions. The molecular and cellular mechanisms by which non-coplanar PCBs and related structures alter local and global Ca2+ signaling properties and the possible short and long-term consequences of these perturbations on neurodevelopment and neurodegeneration are reviewed.
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“Nanomolar concentrations of PCB 95 stabilize ryanodine receptors (RyRs) in the open configuration, increasing Ca 2ϩ release from intracellular stores (Pessah et al., 2010).”
From The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation (2014) · cites this paper as Pessah et al., 2010
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In the citing paper
“Because RyRs are functionally coupled to NMDA receptors (Berridge, 2006;Pessah et al., 2010), our findings suggest that RyRs are required for not only PCB-induced synaptogenesis, but also activity-dependent synaptogenesis, expanding the role for RyRs in neuronal plasticity.”
From The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation (2014) · cites this paper as Pessah et al., 2010
In the citing paper
“NDL PCBs are thought to disrupt normal neurodevelopment via modulation of signaling by biogenic amines, thyroid hormone, and intracellular calcium during critical windows of brain development [ 105 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [105]
In the citing paper
“These are pathways that are also dysregulated in ASD [ 27 , 105 , 123 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [105]
In the citing paper
“PCBs are important endocrine disruptors which, among several other effects, perturb intracellular Ca2+ signalling by promoting Ca2+ entry and by enhancing Ca2+ release from the endoplasmic reticulum through ryanodine receptors [248].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [248]
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Metadata
- Authors
- Pessah, I. N., Cherednichenko, G., & Lein, P. J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Pessah, Isaac N.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 125
- Issue
- 2
- Pages
- 260-285
- ISSN
- 0163-7258 (ISSN-L)
- PMC
- PMC2823855
- OpenAlex
- W2171969201
- Cited by
- 231
- References
- 452
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 12 · 2022: 12 · 2021: 9 · 2020: 18 · 2019: 15 · 2018: 19 · 2017: 22 · 2016: 14 · 2015: 15 · 2014: 19 · 2013: 15 · 2012: 27
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (1 P01-ES11269, P42-ES-04699, P42ES004699, P01ES011269, R01ES014901)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- polychlorinated biphenyls, ryanodine receptor, calcium signaling, developmental neurotoxicity, neurodegeneration, intracellular calcium stores, immune dysfunction, cardiovascular disease
- MeSH terms
- Calcium, Environmental Pollutants, Humans, Polychlorinated Biphenyls, Structure-Activity Relationship, Ryanodine Receptor Calcium Release Channel
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