Involvement of NLRP3/Caspase-1/GSDMD-Dependent pyroptosis in BPA-Induced apoptosis of human neuroblastoma cells.

Abstract

Bisphenol A (BPA) induces neurotoxicity via enhancing cell apoptosis and inflammation potently (effective at nanomolar concentrations), but its mechanisms remain unidentified. In this study, human neuroblastoma cell lines, IMR-32 and SK-N-SH cells, isolated from a male and a female subject, respectively, were exposed to BPA at various concentrations, with epigallocatechin gallate (EGCG, an antioxidant from green tea), Z-YVAD-FMK (a caspase-1 inhibitor), and ICI182.780 [an estrogen receptor (ER) inhibitor] as modulators. The results showed that BPA increased the mRNA levels of IL-18, ASC, GSDMD and protein levels of NLRP3, caspase-1 and GSDMD in both cell lines in a nonlinear manner. Noticeably, the direction of changes in the mRNA levels of caspase-1 and IL-1β were opposite, so did each of them in different cell lines: caspase-1 was enhanced in IMR-32 cells but suppressed in SK-N-SH cells, while IL-1β was suppressed in IMR-32 cells but enhanced in SK-N-SH cells. The level of GSDMD in situ increased along with the leakage of IL-1β, IL-18, caspase-1 and lactate dehydrogenase (LDH). Moreover, all the above effects of BPA were reversed by Z-YVAD-FMK, ICI182.780, and EGCG. Besides, BPA significantly increased reactive oxygen species production, LDH leakage and apoptosis, with reduced cell viability and mitochondrial membrane potential, in both cell lines, whereas Z-YVAD-FMK and ICI182.780 significantly alleviated the induction of Bak1, Bax, Bcl-2 and caspase-3 proteins by BPA. In summary, BPA may induce pyroptosis in neuroblastoma cells through NLRP3/caspase-1/GSDMD pathway, as mediated by ER; caspase-1-dependent pyroptosis may also contribute to BPA-induced apoptosis, an effect alleviated by EGCG.

• Authors: Congcong Wang, Lei Wang, Chengmeng Huang, Yungang Liu, Jian Liu, Hongxuan Kuang, Qihua Pang, Hongyu Han, Ruifang Fan
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 200 Pg. 115042 (06 2022) ISSN: 1873-2968 [Electronic] England
• PMID: 35439536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Benzhydryl Compounds
• GSDMD protein, human
• Inflammasomes
• Interleukin-18
• Intracellular Signaling Peptides and Proteins
• NLR Family, Pyrin Domain-Containing 3 Protein
• Phenols
• Phosphate-Binding Proteins
• Pore Forming Cytotoxic Proteins
• RNA, Messenger
• Caspase 1
• bisphenol A

Topics

• Apoptosis
• Benzhydryl Compounds
• Caspase 1 (metabolism)
• Female
• Humans
• Inflammasomes (metabolism)
• Interleukin-18
• Intracellular Signaling Peptides and Proteins (metabolism)
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Neuroblastoma
• Phenols
• Phosphate-Binding Proteins (metabolism)
• Pore Forming Cytotoxic Proteins
• Pyroptosis
• RNA, Messenger