Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs
- PMID: 22996013
- DOI: 10.1007/s12640-012-9353-4
Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs
Abstract
Bisphenol AF (BPAF), a newly introduced chemical structurally related to bisphenol A, is used extensively in fluoroelastomers and polyesters, and has been known to induce estrogen-dependent responses. However, the toxicity of BPAF is largely unknown except for its endocrine-related effects. In this study, we investigated the neurotoxicity of BPAF and underlying mechanisms of action using hippocampal cell line (HT-22) and mouse primary neuronal cells. We found that BPAF induced apoptosis in both HT-22 and primary neuronal cells. In order to clarify the underlying mechanisms of BPAF-induced apoptosis, various signaling molecules were evaluated. BPAF increased the level of intracellular calcium, followed by the generation of reactive oxygen species (ROS). BPAF upregulated the phosphorylation of mitogen-activated protein kinase: extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-κB. Using specific inhibitors, we confirmed that calcium, ROS, p38, and JNK mediated the BPAF-induced apoptosis. In addition, BPAF inhibited microglial activation in a microglia/neuroblastoma coculture model by the reduction of nitric oxide production. We found that BPAF interrupted the normal physiologic functions of microglia at non-toxic levels. Taken together, our results suggest that BPAF, the substitute of BPA, also have neurotoxic properties.
Similar articles
-
Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-kappaB.J Neurosci Res. 2008 Oct;86(13):2932-42. doi: 10.1002/jnr.21739. J Neurosci Res. 2008. PMID: 18521933
-
Vitamin E suppression of microglial activation is neuroprotective.J Neurosci Res. 2001 Oct 15;66(2):163-70. doi: 10.1002/jnr.1208. J Neurosci Res. 2001. PMID: 11592111 Free PMC article.
-
Bisphenol AF negatively affects oocyte maturation of mouse in vitro through increasing oxidative stress and DNA damage.Chem Biol Interact. 2017 Dec 25;278:222-229. doi: 10.1016/j.cbi.2017.10.030. Epub 2017 Nov 2. Chem Biol Interact. 2017. PMID: 29102535
-
Apoptosis induced by trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways.Arch Toxicol. 2013 Jul;87(7):1273-85. doi: 10.1007/s00204-013-1021-9. Epub 2013 Feb 20. Arch Toxicol. 2013. PMID: 23423712
-
MAPK and NF-κB pathways are involved in bisphenol A-induced TNF-α and IL-6 production in BV2 microglial cells.Inflammation. 2015 Apr;38(2):637-48. doi: 10.1007/s10753-014-9971-5. Inflammation. 2015. PMID: 25047101
Cited by
-
The Ca(2+) channel inhibitor 2-APB reverses β-amyloid-induced LTP deficit in hippocampus by blocking BAX and caspase-3 hyperactivation.Br J Pharmacol. 2015 May;172(9):2273-85. doi: 10.1111/bph.13048. Epub 2015 Feb 27. Br J Pharmacol. 2015. PMID: 25521332 Free PMC article.
-
Gene expression patterns and DNA methylation of neuron and pancreatic β-cell developments in zebrafish embryos treated with bisphenol F and AF.Heliyon. 2024 Jun 27;10(13):e33805. doi: 10.1016/j.heliyon.2024.e33805. eCollection 2024 Jul 15. Heliyon. 2024. PMID: 39050442 Free PMC article.
-
Animal Models and Their Contribution to Our Understanding of the Relationship Between Environments, Epigenetic Modifications, and Behavior.Genes (Basel). 2019 Jan 15;10(1):47. doi: 10.3390/genes10010047. Genes (Basel). 2019. PMID: 30650619 Free PMC article. Review.
-
Inhibition of metabotropic glutamate receptor 5 induces cellular stress through pertussis toxin-sensitive Gi-proteins in murine BV-2 microglia cells.J Neuroinflammation. 2014 Nov 19;11:190. doi: 10.1186/s12974-014-0190-7. J Neuroinflammation. 2014. PMID: 25407356 Free PMC article.
-
The effect of the aquatic contaminants bisphenol-A and PCB-95 on the zebrafish lateral line.Neurotoxicology. 2015 Jan;46:125-36. doi: 10.1016/j.neuro.2014.12.010. Epub 2014 Dec 31. Neurotoxicology. 2015. PMID: 25556122 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous