Bisphenol A induced neuronal apoptosis and enhanced autophagy in vitro through Nrf2/HO-1 and Akt/mTOR pathways
Abstract
Bisphenol A (BPA) was traditionally used in epoxy resins and polycarbonate plastics, but it was found to be harmful to human health due to its endocrine-disrupting effects. It can affect various biological functions of human beings and interfere with brain development. However, the neurotoxic mechanisms of BPA on brain development and associated neurodegeneration remain poorly understood. Here, we reported that BPA (100, 250, 500 μM) inhibited cell viability of neural cells PC12, SH-SY5Y and caused dose-dependent cell death. In addition, BPA exposure increased intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS) levels, decreased mitochondrial membrane potential, reduced the expression of cytochrome c oxidase IV (COX4), downregulated Bcl-2, and initiated apoptosis. Moreover, BPA treatment resulted in the accumulation of intracellular acidic vacuoles and increased the autophagy marker LC3 II to LC3 I ratio. Furthermore, BPA exposure inhibited Nrf2/ HO-1 and AKT/mTOR pathways and mediated cellular oxidative stress, apoptosis, and excessive autophagy, leading to neuronal degeneration. The interactions between oxidative stress, autophagy, and apoptosis during BPA-induced neurotoxicity remain unclear and require further in vivo confirmation.
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BPA and related compounds increase ROS production, promoting neuronal damage and apoptosis.
“BPA and related compounds increase ROS production, thereby promoting neuronal damage and apoptosis (Kobayashi et al., 2020; Shen et al., 2023).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Shen et al., 2023
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ROS, mitochondria and the regulation of autophagy
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FIP200 is required for maintenance and differentiation of postnatal neural stem cells
Wang, C., Liang, C.-C., Bian, Z. C., Zhu, Y., & Guan, J.-L. (2013) · Nature Neuroscience · doi:10.1038/nn.3365 · Cited by 169 · see citing works
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Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms
Hu, F., Li, T., Gong, H., Chen, Z., Jin, Y., Xu, G., & Wang, M. (2017) · Advanced Science · doi:10.1002/advs.201600493 · Cited by 87 · see citing works
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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
“BPA and related compounds increase ROS production, thereby promoting neuronal damage and apoptosis (Kobayashi et al., 2020; Shen et al., 2023).”
- Authors
- Shen, Y., Li, X., Wang, H., Wang, Y., Tao, L., Wang, P., & Zhang, H.
- Affiliations
- Shaoxing University (CN)
- Corresponding author
- Zhang, Heng
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 500
- Pages
- 153678
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W4388948786
- Cited by
- 22
- References
- 4
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 5 · 2023: 1
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- bisphenol A, neurotoxicity, neuronal apoptosis, autophagy, Nrf2/HO-1 pathway, Akt/mTOR signaling, oxidative stress, reactive oxygen species, mitochondrial reactive oxygen species, mitochondrial membrane potential, Bcl-2, LC3, endocrine disruptors, PC12 cells, SH-SY5Y cells
- MeSH terms
- Bisphenol A Compounds, Autophagy, Humans, Neuroblastoma, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Proto-Oncogene Proteins c-akt, NF-E2-Related Factor 2, TOR Serine-Threonine Kinases
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