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Role of the BDNF/TrkB/CREB signaling pathway in the cytotoxicity of bisphenol S in SK‐N‐SH cells
Author(s) -
He Qingzhi,
Zhu Biqi,
Xu Xiaona,
Zeng Huaicai
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22775
Subject(s) - creb , tropomyosin receptor kinase b , neurotrophic factors , neurotoxicity , apoptosis , chemistry , brain derived neurotrophic factor , viability assay , microbiology and biotechnology , tropomyosin receptor kinase a , signal transduction , neurotrophin , biology , biochemistry , receptor , transcription factor , organic chemistry , toxicity , gene
Bisphenol S (BPS) is associated with neurotoxicity, but its molecular mechanisms are unclear. Our aim was to investigate the role of the brain‐derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cAMP‐response element‐binding protein (CREB) signaling pathway in BPS‐induced cytotoxicity in SK‐N‐SH cells. The cells were treated with various concentrations of BPS, and cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and the BDNF, cleaved‐caspase‐3, B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), TrkB, CREB, and phospho‐CREB (p‐CREB) levels were determined. The effects of pretreatment with the TrkB activator 7,8‐dihydroxyflavone (7,8‐DHF) were also explored. BPS decreased SK‐N‐SH cell viability and altered their morphology. Their apoptosis rate was increased, as were the levels of the proapoptotic proteins Bax and cleaved‐caspase‐3, but MMP was decreased. Thus, BPS may induce mitochondria‐dependent apoptosis pathways. BPS also reduced the BDNF, TrkB, and p‐CREB levels, and pretreatment with 7,8‐DHF alleviated its cytotoxic effects. Thus, BPS‐induced cytotoxicity might be mediated by the BDNF/TrkB/CREB signaling pathway.