Disrupted metabolic pathways and potential human diseases induced by bisphenol S.

Although the toxicity of bisphenol S has been studied in some species, the global metabolic network disrupted by bisphenol S remains unclear. To this end, published datasets related to the genes, proteins, and metabolites disturbed by bisphenol S were investigated through omics methods. The dataset revealed that bisphenol S at high concentrations tended to downregulate biomolecules, while low concentrations of bisphenol S tended to enhance metabolic reactions. The results showed that exposure to bisphenol S upregulated estrogen and downregulated androgen metabolism in humans, mice, rats, and zebrafish. Fatty acid metabolism and phospholipid metabolism in mice were upregulated. Reactions in amino acid metabolism were upregulated, with the exception of the suppressive conversion of arginine to ornithine. In zebrafish, fatty acid synthesis was promoted, while nucleotide metabolism was primarily depressed through the downregulation of pyruvate 2-o-phosphotransferase. The interference in amino acid metabolism by bisphenol S could trigger Alzheimer's disease, while its disturbance of glucose metabolism was associated with type II diabetes. Disturbed glycolipid metabolism and vitamin metabolism could induce Alzheimer's disease and diabetes. These findings based on omics data provide scientific insight into the metabolic network regulated by bisphenol S and the diseases triggered by its metabolic disruption.

Systematic stress adaptation of Bacillus subtilis to tetracycline exposure.

To alleviate the harmful effects of antibiotics on the environment and human health, the stress response and molecular network of Bacillus under tetracycline stress were investigated using a proteomics approach. During the exposure process, Bacillus subtilis exhibited a strong adaptation mechanism. Cell membrane and intracellular reactive oxygen species (ROS) level returned to normal after 5 h. A total of 312 upregulated and 65 downregulated proteins were identified, mainly involved in metabolism and the synthesis of ribosomes, DNA, and RNA. After tetracycline exposure, the core metabolism network was accelerated to supply precursors for the synthesis of DNA, RNA, proteins, peptidoglycans, and saturated fatty acids that were involved in ribosome protection, and strengthened the cell wall and cell membrane. The signal transduction pathways involved were analyzed in association with the stress response of B. subtilis at 15 min of exposure to tetracycline. The primary damage to the ribosome by tetracycline activated a series of response proteins. Antitoxin and heat-shock proteins were activated for the global regulation of transcription and metabolism. Trigger factor Tig was upregulated to ensure proper initiation of transcription and aerobic respiration. Temperature-sensor protein VicR from the two-component system was used by the cell to regulate the composition of the cell wall and cell membrane. The over-consumption of metabolites, such as phosphoribosyl diphosphate (PRPP), purine nucleoside triphosphate (GTP), and acetyl-CoA forced the cells to assimilate more sugar for glycolysis. To this end, methyl-accepting chemotaxis proteins (MCPs) and sugar transportation protein PtsG were upregulated, simultaneously. Ultimately, peroxidase was activated to eliminate the redundant ROS, to minimize cell damage. These findings presented a system-level understanding of adaption processes of bacteria to antibiotic stress.

Bisphenol A degradation pathway and associated metabolic networks in Escherichia coli harboring the gene encoding CYP450.

Although bisphenol A (BPA) can be transformed by CYP450, the metabolic networks involved in regulating the transformation processes are not clear. In this study, Escherichia coli harboring the gene encoding CYP450 was used as a model to elucidate the BPA degradation pathway and the associated metabolic network using a proteomic approach. The results showed that CYP450 promotes the transformation of BPA, generating 1,2-bis(4-hydroxyphenyl)-2-propanol and 2,2-bis(4-hydroxyphenyl)-1-propanol, with hydroquinone and 4-(2-hydroxypropan-2-yl)phenol formed in another pathway. The DNA adducts formed by 1,4-benzoquinone were reduced, and CYP450 played a positive role in cellular homeostasis by promoting the transformation of BPA and mismatch repair. An increase in the synthesis of cell membrane lipids was observed after dislodging BPA. BPA disturbed folate metabolism by decreasing the abundance of dihydrofolate reductase, which inhibited microbial metabolism in the absence of CYP450. The findings of this study revealed the molecular mechanism associated with the metabolic network responsible for pollutant tolerance and degradation.

A goose-type lysozyme gene in Japanese scallop (Mizuhopecten yessoensis): cDNA cloning, mRNA expression and promoter sequence analysis.

Lysozyme is an important component of the immune response against bacteria that is characterized by its ability to break down bacterial cell-walls. We constructed a high-quality cDNA library from mantle tissue of adult Japanese scallop (Mizuhopecten yessoensis). The EST which is high homology with g-type lysozyme genes of other species was found in the cDNA library. In the present study, the complete express sequence of g-type lysozyme genes from Japanese scallop (designated as MyLysoG) was directly obtained by PCR. The complete sequence of MyLysoG cDNA consisted of a 5' untranslated region (UTR) of 25 bp, an open reading frame (ORF) of 606 bp, and a 3' UTR of 100 bp with one polyadenylation signal (AATAAA). The deduced amino acids of MyLysoG were 201 amino acids with a putative signal peptide of 18 amino acid residues. It shared the sequence similarity and the common structure features with the g-type lysozyme from other species. Quantitative reverse trancriptase real-time PCR (qRT-PCR) assay demonstrated that mRNA transcripts of g-type lysozyme could be detected in various tissues of unchallenged scallop, and the highest expression of MyLysoG was detected in hepatopancreas tissue. The temporal expression of MyLysoG in hemolymph after Vibrio anguillarum challenge was up-regulated and reached the maximum level at 3h post stimulation, and then dropped back to the original level even lower than the control group. Furthermore, a 978 bp of 5'-flanking sequence of MyLysoG was identified by genome walking, and several potential transcription factor binding sites (TFBS) were detected in the putative promoter region. One part of the MyLysoG promoter region contains nine sites of SNPs and three sites of insert-deletion (indel) polymorphisms, and these mutations were found organize into two haplotypes. The two haplotypes were associated with different TFBS. The haplotypes could be selected to analyze the transcriptional-level control of scallop g-type lysozyme gene and the scallop immune system.

A selenium-dependent glutathione peroxidase in the Japanese scallop, Mizuhopecten yessoensis: cDNA cloning, promoter sequence analysis and mRNA expression.

Glutathione peroxidase (GPx) is an antioxidant enzyme that protects cells from oxidative damage in the innate immune responses against bacterial infections. GPx is also involved in immune defenses. In this study, we report cloning and characterization of a GPx (designated as MyGPx) coding sequences and promoter from Japanese scallop, Mizuhopecten yessoensis. The full-length 1081 nt MyGPx mRNA contained a 28 nt 5' untranslated region (UTR), a 603 nt open reading frame and a 450 nt 3' UTR containing a polyadenylation signal (AATAAA). Multiple sequence alignment revealed that amino acids essential to enzymatic function of MyGPx proteins were highly conserved. A 1628 nt 5'-flanking sequence of MyGPx was identified by genome walking. Here, several potential transcription factor binding sites were detected in the putative promoter region, and nine single nucleotide polymorphisms (SNPs) were found in the 5' sequence flanking the promoter region. Quantitative Real time PCR (qRT-PCR) was employed to measure GPx mRNA expression in adult tissues and monitor mRNA expression patterns during embryonic development and following stimulation by the bacteria Vibrillo anguillarum. Collectively, the results suggest that MyGPx fulfills an important function during M. yessoensis development and may be an important immune effector in adult molluscs.