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Cited by 27Effects and risks of endocrine disrupting chemicalsToxic Organic Pollutants ImpactMitochondrial Function and Pathology

The role of Ca2+ imbalance in the induction of acute oxidative stress and cytotoxicity in cultured rat cerebellar granule cells challenged with Tetrabromobisphenol A

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Zieminska, Elzbieta, Lenart, Jacek, Diamandakis, Dominik, Lazarewicz, Jerzy W.·2017·Neurochemical Research
DOI 10.1007/s11064-016-2075-xPMC PMC5357503
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Abstract

Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca 2+ ] i ), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (∆Ψm) were measured fluorometrically during the exposure. The intracellular glutathione (GSH) and catalase activity were determined after the incubation; cell viability was evaluated 24 h later. TBBPA concentration-dependently increased [Ca 2+ ] i and ROS production, and reduced GSH content, catalase activity, ∆Ψm and neuronal viability. The combination of NMDA and ryanodine receptor antagonists, MK-801 and bastadin 12 with ryanodine, respectively, prevented Ca 2+ transients and partially reduced cytotoxicity induced by TBBPA at both concentrations. The antagonists also completely inhibited oxidative stress and depolarization of mitochondria evoked by 10 µM TBBPA, whereas these effects were only partially reduced in the 25 µM TBBPA treatment. Free radical scavengers prevented TBBPA-induced development of oxidative stress and improved CGC viability without having any effect on the rises in Ca 2+ and drop in ∆Ψm. The co-administration of scavengers with NMDA and ryanodine receptor antagonists provided almost complete neuroprotection. These results indicate that Ca 2+ imbalance and oxidative stress both mediate acute toxicity of TBBPA in CGC. At 10 µM TBBPA Ca 2+ imbalance is a primary event, inducing oxidative stress, depolarization of mitochondria and cytotoxicity, whilst at a concentration of 25 µM TBBPA an additional Ca 2+ -independent portion of oxidative stress and cytotoxicity emerges.

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Cited by

Sorted by citations

Authors
Zieminska, E., Lenart, J., Diamandakis, D., & Lazarewicz, J. W.
Affiliations
Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
ORCID
Lazarewicz, Jerzy W.
Venue
Neurochemical Research
Publisher
Springer Science and Business Media LLC
Published
2016-10-07
Volume
42
Issue
3
Pages
777-787
ISSN
  • 0364-3190 (ISSN-L)
  • 1573-6903
DOI
10.1007/s11064-016-2075-x
PMC
PMC5357503
OpenAlex
W2527785640
Cited by
27
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 1
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurochemical Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
The Polish National Science Centre (2012/05/B/NZ7/03225)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
tetrabromobisphenol A, calcium imbalance, calcium transients, oxidative stress, cytotoxicity, cerebellar granule cells, reactive oxygen species, mitochondrial depolarization, glutathione, catalase, NMDA receptor antagonists, MK-801, radical scavengers, neuroprotection, brominated flame retardants, neurotoxicity
MeSH terms
Mitochondrial Permeability Transition Pore, Animals, Calcium, Calcium Channel Blockers, Cells, Cultured, Cerebellum, Cytotoxins, Environmental Pollutants, Flame Retardants, Neurons, Polybrominated Biphenyls, Free Radical Scavengers, Receptors, N-Methyl-D-Aspartate, Cyclosporine, Rats, Wistar, Reactive Oxygen Species, Oxidative Stress, Mitochondrial Membrane Transport Proteins, Membrane Potential, Mitochondrial, Primary Cell Culture

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