Fluorene‑9‑bisphenol‑associated endoplasmic reticulum stress linked to oxidative stress, apoptosis and autophagy in...

Fluorene-9-bisphenol (BHPF), an alternative to bisphenol A (BPA), is widely used to make polyester polymers and serves as an important organic intermediate in synthetic plastics. While diverse toxic effects of BHPF have been documented in the literature, its effects on neurons, potential neurotoxicity, and underlying molecular mechanisms remain unclear. In this study, we reported that BHPF (10, 25 µM) inhibited neuronal SH-SY5Y cell viability, increased lactate dehydrogenase (LDH) release, and induced cell death in a dose-dependent manner. BHPF exposure increased intracellular reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) levels, decreased mitochondrial membrane potential, reduced the expression of cytochrome C oxidase subunit 4 (COX4) and mitochondrial protein 1 (MFN1), but upregulated Bax, Caspase-3, Caspase-8 and initiated apoptosis. In addition, BHPF treatment led to the accumulation of acidic vacuoles in the cells and increased the expression of autophagy regulatory proteins, including Beclin-1, LC3II, ATG5 and p62. Moreover, BHPF could trigger endoplasmic reticulum stress (ER stress), and ER stress inhibitor taurodeoxycholate (TUDCA) reversed the BHPF-induced oxidative stress, apoptosis and autophagy. Thus, our in vitro data indicate that ER stress may be linked to the oxidative stress, apoptosis, and autophagy observed in nerve cells following BHPF exposure. These findings offer preliminary insights into cellular processes that could help elucidate the potential role of nerve cells in BHPF-associated degenerative diseases.