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Bisphenol A and its substitutes regulate human B cell survival via Nrf2 expression
Ju-Won Jang1, Jae-Wook Lee1, Yeo Dae Yoon2
1Department of Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea.
Environmental Pollution (Barking, Essex : 1987)
|February 7, 2020
Summary
Bisphenol A (BPA) and its substitutes cause B cell damage via oxidative stress. The Nrf2 pathway protects B cells from this harm, suggesting substitutes may be safer than BPA.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- B cells are crucial for immune responses and disease control.
- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates antioxidant genes, protecting cells from oxidative stress.
- Bisphenol A (BPA) and its substitutes raise concerns regarding physiological safety.
Purpose of the Study:
- To investigate the impact of BPA and its substitutes on B cell viability.
- To explore the role of Nrf2 induction in mediating cellular responses to BPA and its substitutes.
- To compare the cytotoxicity of BPA with that of its substitutes in human B lymphoblast cells.
Main Methods:
- Utilized WiL2-NS human B lymphoblast cells.
- Assessed cytotoxicity using MTT, CellTiter-Glo, trypan blue, and propidium iodide assays.
- Measured reactive oxygen species (ROS) production and gene expression of antioxidant enzymes.
- Employed Nrf2-knockdown (KD) and overexpression models.
Main Results:
- BPA exhibited higher cytotoxicity than its substitutes.
- Both BPA and its substitutes induced significant cytotoxicity and ROS production, which were mitigated by N-acetylcysteine (NAC).
- BPA treatment upregulated Nrf2 and antioxidant enzyme gene expression (HO-1, catalase, SOD1/2).
- Nrf2 knockdown enhanced BPA/substitute-induced cytotoxicity, while Nrf2 overexpression reduced it.
Conclusions:
- Nrf2 activation protects B cells from BPA and substitute-induced cytotoxicity, primarily through mitigating ROS production.
- BPA substitutes demonstrate lower B cell cytotoxicity compared to BPA.
- Further comprehensive evaluations are recommended before replacing BPA with substitutes in manufacturing.
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