TBBPA causes apoptosis in grass carp hepatocytes involving destroyed ER-mitochondrial function

Abstract

Tetrabromobisphenol A (TBBPA) is the most-produced brominated flame retardant, which can be found in various industrial and household products. Studies have shown that TBBPA has hepatotoxicity, and could pose a risk to aquatic animals. The endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in cells, the homeostasis and orchestrated interactions of which are crucial to maintaining cellular function. The aim of this study was to explore the involvement of ER-mitochondria crosstalk in TBBPA-induced toxicity in aquatic animals' hepatocytes. Herein, we exposed grass carp hepatocytes (L8824 cells) to different concentrations of TBBPA. Our experimental results suggested that TBBPA exposure suppressed cell viability and caused apoptosis of L8824 cells. TBBPA treatment upregulated expressions of ER stress markers, increased reactive oxygen species (ROS) and mitochondrial Ca²⁺ levels, and reduced mitochondrial membrane potential (MMP) in L8824 cells. However, the pretreatment of 2-aminoethoxydiphenyl borate (2-APB) could alleviate TBBPA-induced cell apoptosis, ER stress, and mitochondrial dysfunction. Additionally, 2-APB pretreat relieved ER-mitochondrial contact and the expression of ER-mitochondrial function-related genes induced by high-dose TBBPA. Taken together, these results indicated that TBBPA caused grass carp hepatocyte apoptosis by destroying ER-mitochondrial crosstalk.

Keywords: Apoptosis; ER-mitochondrial function; Grass carp; Tetrabromobisphenol A.