Neurotoxic Effects of Bisphenol AF on Calcium-Induced ROS and MAPKs

Neurons 0301 basic medicine Molecular Structure MAP Kinase Signaling System NF-kappa B Apoptosis Nerve Tissue Proteins Nitric Oxide Hippocampus Coculture Techniques Cell Line 3. Good health Enzyme Activation Mice Neuroblastoma 03 medical and health sciences Cell Line, Tumor Animals Calcium Signaling Microglia Benzhydryl Compounds Mitogen-Activated Protein Kinases Cells, Cultured
DOI: 10.1007/s12640-012-9353-4 Publication Date: 2012-09-20T03:54:51Z
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (39)
CITATIONS (70)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....