The Toxic Effects of Tetrachlorobisphenol A in Saccharomyces cerevisiae Cells via Metabolic Interference

Abstract

Tetrachlorobisphenol A (TCBPA) is a common flame retardant detected in different environments. However, its toxic effects on animals and humans are not fully understood. Here, the differential intracellular metabolites and associated gene expression were used to clarify the metabolic interference of TCBPA in Saccharomyces cerevisiae, a simple eukaryotic model organism. The results indicated that TCBPA treatment promoted the glycolysis pathway but inhibited the tricarboxylic acid (TCA) cycle, energy metabolism and the hexose monophosphate pathway (HMP) pathway. Thus, the HMP pathway produced less reducing power, leading to the accumulation of reactive oxygen species (ROS) and aggravation of oxidative damage. Accordingly, the carbon flux was channelled into the accumulation of fatty acids, amino acids and glycerol instead of biomass production and energy metabolism. The accumulation of these metabolites might serve a protective function against TCBPA stress by maintaining the cell membrane integrity or providing a stable intracellular environment in S. cerevisiae. These results enhance our knowledge of the toxic effects of TCBPA on S. cerevisiae via metabolic interference and pave the way for clarification of the mechanisms underlying TCBPA toxicity in animals and humans.

An integrative cellular metabolomic study reveals downregulated tricarboxylic acid cycle and potential biomarkers induced by tetrabromobisphenol A in human lung A549 cells

“…Recently, an in vitro study revealed that high levels of TBBPA could cause morphological and ultrastructure changes including dilated smooth endoplasmic reticulum and extensively injured mitochondria in A549 cells, which may correlate with cells' excessive ROS generation 19 . Moreover, TCBPA treatment, a derivative of bisphenol A, was found to inhibit the TCA cycle and decrease the expression of three key TCA cycle genes ( CIT1 , KGD1 , and IDH1 ) in Saccharomyces cerevisiae cells 27 . In addition to suppressing TCA cycle activity, TCBPA was found to promote glycolysis and inhibit ATP production and the hexose monophosphate shunt.…”

“…19 Moreover, TCBPA treatment, a derivative of bisphenol A, was found to inhibit the TCA cycle and decrease the expression of three key TCA cycle genes (CIT1, KGD1, and IDH1) in Saccharomyces cerevisiae cells. 27 In addition to suppressing TCA cycle activity, TCBPA was found to promote glycolysis and inhibit ATP production and the hexose monophosphate shunt. In agreement with recent reports, we observed decreased levels of metabolites involved in the TCA cycle including citrate, fumarate, malate, and alpha-ketoglutarate in the 50 μM TBBPA-treated A549 cells using LC-MS.…”

“…TBBPA exposure can significantly decrease the viability of human cell lines, such as breast cancer cell, neural stem cell, peripheral blood mononuclear cell, osteoblastic MC3T3-E1 cells, and pulmonary epithelial cells. 20,[24][25][26][27] Specifically, previous transcriptomic analysis of TBBPA-treated epithelial cells has shown prominent effects in NF-κB, TNF signaling, toll-like receptor, MAPK signaling, and B-cell receptor pathways affecting cell proliferation and cell differentiation, as well as inflammatory response. 20 Furthermore, previous in vitro studies have shown decreased ATP levels as well as increased reactive oxygen species (ROS) in response to TBBPA exposure.…”

Nanoscale Configuration of Clay-Interlayer Chemistry: A Precursor to Enhancing Flame Retardant Properties

“…The fact that gaseous toxicity release surpasses the ability of flame retardants to suppress fires is a major concern [4] and has shown to persist inside teaching classrooms [20] and college dormitories [21]. Poly-brominated and other halogen-based retardants are shown to be linked to bioaccumulation [22] with child developmental problems effecting child IQ performance, development and intelligence impacting neurologic function in children [23], weakening immune systems through Immunotoxicity [24], reproducibility [25], metabolic [26] and respiratory [27] interference. Such health risks also include harm to wildlife [28].…”