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.