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

Juan Tian,Fengbang Wang,Hao Li,Zhihua Ji,Maoyong Song

doi:10.1038/s41598-017-02939-y

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.

Highlights

Saccharomyces cerevisiae, which is a commonly used eukaryotic model microorganism, has some advantages compared with animals and humans, such as its simple structure, fully interpreted genetic background and ease of manipulation
Considering that Tetrachlorobisphenol A (TCBPA) might cause several metabolic perturbations and might be associated with many genes, mRNAs, proteins and metabolites, a gas chromatography-mass spectrometry (GC-MS)-based metabolomics strategy combined with multivariate statistical and gene expression analyses was used to determine the TCBPA exposure-associated intracellular metabolic changes in S. cerevisiae
The addition of an intermediate or high concentration of TCBPA inhibited the growth of yeast cells (P < 0.05), and the inhibition degree increased as the TCBPA concentration increased (Fig. 1a)

Summary

Introduction

Saccharomyces cerevisiae, which is a commonly used eukaryotic model microorganism, has some advantages compared with animals and humans, such as its simple structure, fully interpreted genetic background and ease of manipulation. In our previous studies using a gas chromatography-mass spectrometry (GC-MS)-based metabolomics strategy, it was found that external stress could cause intracellular metabolite changes in S. cerevisiae[21, 22]. Considering that TCBPA might cause several metabolic perturbations and might be associated with many genes, mRNAs, proteins and metabolites, a GC-MS-based metabolomics strategy combined with multivariate statistical and gene expression analyses was used to determine the TCBPA exposure-associated intracellular metabolic changes in S. cerevisiae. These results helped elucidate the mechanisms involved in TCBPA toxicity to yeast and may indicate further effects in other animals and humans

Methods

Results

Conclusion