The sarcoplasmic–endoplasmic reticulum Ca2+-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD)
Abstract
Hexabromocyclododecane (HBCD) is a widely utilised brominated flame retardant (BFR). It has been shown to bio-accumulate within organisms, including man, and possibly cause neurological disorders. The acute neurotoxicity of HBCD, and six other unrelated BFRs, were assessed in SH-SY5Y human neuroblastoma cells by 24h viability assays and HBCD proved to be the most lethal (LC50, 3μM). In addition, the effects of these BFRs were also assessed for their potency at inhibiting the sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) derived from the SH-SY5Y cells and again HBCD was the most potent (IC50, 2.7μM). The data for the other BFRs tested showed a direct correlation (coefficient 0.94) between the potencies of inducing cell death and inhibiting the Ca(2+) ATPase, indicating that SERCA is likely to be the molecular target for acute toxicity. Mechanistic studies of HBCD on the Ca(2+) ATPase suggest that it affects ATP binding, phosphorylation as well as the E2 to E1 transition step.
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TBBPA induces dose-dependent cytotoxicity in cerebellar granule cells, attributed to disturbed calcium currents together with increased oxidative stress.
“TBBPA, for instance, induces dose-dependent cytotoxicity in cerebellar granule cells, an effect attributed to disturbed calcium currents together with increased oxidative stress (Al-Mousa and Michelangeli, 2014; Reistad et al., 2007; Zieminska et al., 2017).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Al-Mousa and Michelangeli, 2014
Reduced expression of synaptophysin and PSD-95 is closely associated with impaired learning and memory as well as with psychiatric vulnerability.
“Reduced expression of these proteins is closely associated with impaired learning and memory as well as with psychiatric vulnerability (Al-Mousa and Michelangeli, 2014; Li et al., 2017).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Al-Mousa and Michelangeli, 2014
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Seralini, G.-E., & Jungers, G. (2021) · Toxicology Reports · doi:10.1016/j.toxrep.2021.07.014 · Cited by 57 · see citing works
Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
- Authors
- Al-Mousa, F., & Michelangeli, F.
- Affiliations
- University of Birmingham (GB)
- Corresponding author
- Michelangeli, Francesco
- Venue
- Chemico-Biological Interactions
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 207
- Pages
- 1-6
- ISSN
- 0009-2797 (ISSN-L)
- OpenAlex
- W2036594407
- Cited by
- 33
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemico-Biological Interactions (publishedVersion)
- PubMed (publishedVersion)
- ChesterRep (University of Chester) (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Materials Science › Polymers and Plastics › Flame retardant materials and properties
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- hexabromocyclododecane, brominated flame retardants, SERCA, sarco/endoplasmic reticulum Ca2+-ATPase, acute neurotoxicity, SH-SY5Y cells, molecular targets, cell viability, ATP binding, phosphorylation, bioaccumulation
- MeSH terms
- Adenosine Triphosphate, Calcium, Cell Survival, Flame Retardants, Fluorescence, Humans, Hydrocarbons, Brominated, Magnesium, Phosphorylation, Fluorescein-5-isothiocyanate, Toxicity Tests, Acute, Cell Line, Tumor, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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