Effects of novel brominated flame retardant TBBPA on human airway epithelial cell (A549) in vitro and proteome profiling

Abstract

The cellular toxicity response of human airway epithelial cells (A549) to tetrabromobisphenol (TBBPA) was assessed in vitro. Cell viability, levels of intracellular reactive oxygen species (ROS), lipid peroxidation (MDA), and caspase-3 activity were determined after A549 treated with varying concentrations of TBBPA. A comparative proteomic analysis was performed in cells treated with different concentrations of TBBPA (0, 10, and 40 μg/mL). Two-way anova analysis showed that cell viability was significantly decreased after treatment by TBBPA with a concentration of 16 μg/mL for 48 hr, however, the caspase-3 activities, ROS generation, and MDA content increased. Ultrastructural observation revealed that the cell was morphological damaged after exposure to 64 μg/mL TBBPA, with mitochondria seriously injured and the smooth endoplasmic reticulum dilated. There was a good correlation between ROS generation and mitochondrial dysfunction. Seventeen differentially expressed proteins involved in various biological processes were identified. These findings provide a basis for understanding the mechanisms of cell dysfunction and perturbation of antioxidant status induced by additive flame retardant on airway epithelial cells.

Transcriptomic analyses of human bronchial epithelial cells BEAS‐2B exposed to brominated flame retardant (tetrabromobisphenol A)

“…TBBPA is a cytotoxicant that can interfere with cellular signaling pathways, reducing cell viability and proliferation . Previous studies demonstrated that the PBDEs including derivatives reduced cell viability in various cell lines . In agreement with these studies, we found that TBBPA at concentrations ranging from 8 to 64 μg·mL −1 significantly reduced the viability of BEAS‐2B cells at the time points of 12 h, 24 h, and 48 h. The decrease of cell viability treated by TBBPA was in agreement with those reported on other biphenyl organic pollutants.…”

“…25 Previous studies demonstrated that the PBDEs including derivatives reduced cell viability in various cell lines. [37][38][39] In agreement with these studies, we found that TBBPA at concentrations ranging from 8 to 64 μgÁmL −1 significantly reduced the viability of BEAS-2B cells at the time points of 12 h, 24 h, and 48 h. The decrease of cell viability treated by TBBPA was in agreement with those reported on other biphenyl organic pollutants. For example, a dose-dependent decrease was observed on human vascular endothelial cells (HUVECs) exposed to mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) at several sublethal concentrations.…”

“…Abnormalities in any of these functions might contribute to the cardiovascular and respiratory disease . Increasing evidence suggests that gene expression and signal transduction would be affected, and biological macromolecules as well as subcellular structures would be damaged . The present study showed that the expression of chemokine gene ( Ccl3 and Ccl4 ) and inflammatory signaling genes ( Lilrb4a and Lilr4b ) increased obviously induced by TBBPA (Table and Figure ), which indicated that cells in TBBPA treated group might undergo immune balance and initiate inflammatory signaling transduction.…”

“…In the morphological observation, an obvious phenomenon was found in TBBPA treated group that the cells were extensively necrotic, and especially mitochondria, multi‐lamellar bodies well and the macrostructure of the cell was obviously deformed (Figure C). Wu et al have reported similar findings that TBBPA could deform the macrostructure of the cell especially mitochondria, multi‐lamellar bodies well in A549 cell line through G2 arrest and sever mitotic spindle aberration.…”

Effects of polystyrene microbeads on cytotoxicity and transcriptomic profiles in human Caco‐2 cells

“…Malondialdehyde (MDA) was showed as nmol thiobarbituric acid‐reactive substance (TBARS) per mg protein. Total protein was assayed utilizing commercial BCA protein kit (Sangon, Shanghai, China) on the basis of the manufacturer's guidances …”