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The lipid metabolism alteration of three spirocyclic tetramic acids on zebrafish (Danio rerio) embryos
2019
Zhang, Jie | Qian, Le | Teng, Miaomiao | Mu, Xiyan | Qi, Suzhen | Chen, Xiangguang | Zhou, Yimeng | Cheng, Yi | Pang, Sen | Li, Xuefeng | Wang, Chengju
Spirocyclic tetramic acids are widely used in controlling phytophagous mite species throughout the world. the data set is incomplete and provides insufficient evidence for drawing the same conclusion for fish. To fill the gap whether these acaricides alter lipid metabolism on vertebrates, zebrafish embryos exposed to a series concentration of pesticides, the developmental effects, enzyme activities and levels of gene expression were assessed, battery of biomarker utilized by the integrated biomarker response (IBRv2) model. The 96 h-LC₅₀ of spirodiclofen, spiromesifen and spirotetramat were 0.14, 0.12 and 5.94 mg/L, respectively. Yolk sac deformity, pericardial edema, spinal curvature and tail malformation were observed. Three spirocyclic acids were unfavouring the lipid accumulation of by inhibited the acetyl-CoA carboxylase (ACC), fatty acid synthesis (FAS), fatty acid binding proteins (FABP2) and lipoprotein lipase (LPL) activity. The total cholesterol (TCHO) level significantly decreased in the 0.072 mg/L spirodiclofen group and 0.015 and 0.030 mg/L in the spiromesifen groups. No expected change in spirotetramat group on the TCHO and triglycerides (TGs) levels for any of the treatments. The mRNA levels of the genes related to lipid metabolism also significantly altered. In both spirodiclofen and spiromesifen, ACC achieved the highest scores among a battery of biomarkers using integrated biomarker response (IBRv2). The results suggest that spiromesifen was the most toxic for embryos development and spirodiclofen was the most toxic for lipid metabolism in embryos. The 0.07 mg/L of spirodiclofen, 0.05 mg/L of spiromesifen and 2.00 mg/L would cause malformation on zebrafish embryos. This study will provide new insight that fatty acid metabolism may be a suitable biomarker for the spirocyclic tetramic acids in fish species.
Show more [+] Less [-]Effect modification by apoptosis-related gene polymorphisms on the associations of phthalate exposure with spermatozoa apoptosis and semen quality
2017
Yang, Pan | Gong, Ya-Jie | Wang, Yi-Xin | Liang, Xin-Xiu | Liu, Qing | Liu, Chong | Chen, Ying-Jun | Sun, Li | Lu, Wen-Qing | Zeng, Qiang
Human studies indicate that phthalate exposure is associated with adverse male reproductive health, and this association may be modified by genetic polymorphisms.We investigated whether apoptosis-related gene polymorphisms modified the associations of phthalate exposure with spermatozoa apoptosis and semen quality.In this Chinese population who sought for semen examination in an infertility clinic, we measured 8 phthalate metabolites in two urine samples to assess the individual's exposure levels. Apoptosis-related gene (Fas, FasL, and caspase3) polymorphisms were performed by real-time PCR. Spermatozoa apoptosis and semen quality parameters were evaluated by Annexin V/PI assay and computer-aided semen analysis, respectively.We found that Fas rs2234767, FasL rs763110, and caspase3 rs12108497 gene polymorphisms significantly modified the associations between urinary phthalate metabolites and spermatozoa apoptosis. For example, urinary monobutyl phthalate (MBP) associated with an increased percentage of Annexin V⁺/PI⁻ spermatozoa of 25.11% (95% CI: 4.08%, 50.53%) were only observed among men with CT/TT genotype of FasL rs763110. In addition, we found that caspase3 rs12108497 gene polymorphisms significantly modified the associations of urinary mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with decreased sperm concentration and sperm count (both p-values for interactions = 0.02).Our results provided the first evidence that apoptosis-related gene polymorphisms might contribute to the effects of phthalate exposure on male reproductive health.
Show more [+] Less [-]Regulatory loop between lncRNA FAS-AS1 and DNMT3b controls FAS expression in hydroquinone-treated TK6 cells and benzene-exposed workers
2020
Yuan, Qian | Zhang, Haiqiao | Pan, Zhijie | Ling, Xiaoxuan | Wu, Minhua | Gui, Zhiming | Chen, Jialong | Peng, Jianming | Liu, Zhidong | Tan, Qiang | Huang, Dongsheng | Xiu, Liangchang | Chen, Wen | Shi, Zhizhen | Liu, Linhua
Hydroquinone (HQ), one of the main metabolites of benzene, is a well-known human leukemogen. However, the specific mechanism of how benzene or HQ contributes to the development of leukemia is unknown. In a previous study, we demonstrated the upregulation of DNA methyltransferase (DNMT) expression in HQ-induced malignant transformed TK6 (HQ-TK6) cells. Here, we investigated whether a regulatory loop between the long noncoding RNA FAS-AS1 and DNMT3b exists in HQ-TK6 cells and benzene-exposed workers. We found that the expression of FAS-AS1 was downregulated in HQ-TK6 cells and workers exposed to benzene longer than 1.5 years via histone acetylation, and FAS-AS1 expression was negatively correlated with the time of benzene exposure. Restoration of FAS-AS1 in HQ-TK6 cells promoted apoptosis and inhibited tumorigenicity in female nude mice. Interestingly, treatment with a DNMT inhibitor (5-aza-2-deoxycytidine), histone deacetylase inhibitor (trichostatin A), or DNMT3b knockout led to increased FAS-AS1 through increased H3K27ac protein expression in HQ-TK6 cells, and DNMT3b knockout decreased H3K27ac and DNMT3b enrichment to the FAS-AS1 promoter region, which suggested that DNMT3b and/or histone acetylation involve FAS-AS1 expression. Importantly, restoration of FAS-AS1 resulted in reduced expression of DNMT3b and SIRT1 and increased expression of FAS in both HQ-TK6 cells and xenograft tissues. Moreover, the average DNMT3b expression in 17 paired workers exposed to benzene within 1.5 years was decreased, but that of the remaining 103 paired workers with longer exposure times was increased. Conversely, DNMT3b was negatively correlated with FAS-AS1 expression. Both FAS-AS1 and DNMT3b influenced the enrichment of H3K27ac in the FAS promoter region by regulating the expression of SIRT1, consequently upregulating FAS expression. Taken together, these observations demonstrate crosstalk between FAS-AS1 and DNMT3b via a mutual inhibition loop and indicate a new mechanism by which FAS-AS1 regulates the expression of FAS in benzene-related carcinogenesis.
Show more [+] Less [-]Waterborne Cu exposure increased lipid deposition and lipogenesis by affecting Wnt/β-catenin pathway and the β-catenin acetylation levels of grass carp Ctenopharyngodon idella
2020
Xu, Yi-Chuang | Xu, Yi-Huan | Zhao, Tao | Wu, Li-Xiang | Yang, Shui-Bo | Luo, Zhi
Lipid metabolism could be used as a biomarker for environmental monitoring of metal pollution, including Cu. Given the potential role of the Wnt/β-catenin signaling pathway and acetylation in lipid metabolism, the aim of this study was to investigate the mechanism of Wnt signaling and acetylation mediating Cu-induced lipogenesis. Grass carp Ctenopharyngodon idella, widely distributed freshwater teleost, were used as the model. We found that waterborne Cu exposure increased the accumulation of Cu and lipid, up-regulated lipogenesis, suppressed Wnt signaling, reduced β-catenin protein level and its nuclear location, reduced the sirt1 mRNA levels and up-regulated the β-catenin acetylation level. Further investigation found that Cu up-regulated lipogenesis through Wnt/β-catenin pathway; Cu regulated the β-catenin acetylation, and K311 was the key acetylated residue after Cu incubation. SIRT1 mediated Cu-induced changes of acetylated β-catenin and played an essential role in nuclear accumulation of β-catenin and Cu-induced lipogenesis. Cu facilitated lipid accumulation via the regulation of Wnt pathway by SIRT1. For the first time, our study uncovered the novel mechanism for Wnt/β-catenin pathway and β-catenin acetylation levels mediating Cu-induced lipid deposition, which provided insights into the association between Cu exposure and lipid metabolism in fish and had important environmental implications for monitoring metal pollution in the water by using new biomarkers involved in lipid metabolism.
Show more [+] Less [-]Glyphosate-induced lipid metabolism disorder contributes to hepatotoxicity in juvenile common carp
2021
Liu, Jingbo | Dong, Chenyu | Zhai, Zhenzhen | Tang, Liang | Wang, Lin
Residues of glyphosate (GLY) are widely detected in aquatic systems, raising potential environmental threats and public health concerns, but the mechanism underlying GLY-induced hepatotoxicity in fish has not been fully elucidated yet. This study was designed to explore the hepatotoxic mechanism using juvenile common carp exposed to GLY for 45 d, and plasma and liver samples were collected at 15 d, 30 d, and 45 d to analyze the assays. First, GLY-induced hepatic damage was confirmed by serum liver damage biomarker and hepatic histopathological analysis. Next, changes in oxidative stress biomarkers, gene expression levels of pro- and anti-inflammatory cytokines, and lipid metabolism-related parameters in collected samples were analyzed to clarify their roles in GLY-induced hepatic damage. Data showed that oxidative stress was an early event during GLY exposure, followed by hepatic inflammatory response. Lipid metabolism disorder was a late event during GLY exposure, as evidenced by overproduced hepatic free fatty acids, enhanced lipogenesis-related gene expression levels, reduced lipolysis-related gene expression levels, and resultant hepatic lipid accumulation. Collectively, these findings demonstrate that GLY induces hepatotoxicity in fish through involvement of oxidative stress, inflammatory response, and lipid metabolism disorder, which are intimately interrelated with each other during GLY exposure.
Show more [+] Less [-]Environmentally relevant concentrations of oxytetracycline and copper increased liver lipid deposition through inducing oxidative stress and mitochondria dysfunction in grass carp Ctenopharyngodon idella
2021
Xu, Yi-Huan | Hogstrand, Christer | Xu, Yi-Chuang | Zhao, Tao | Zheng, Hua | Luo, Zhi
Oxytetracycline (OTC) and Cu are prevalent in aquatic ecosystems and their pollution are issues of serious concern. The present working hypothesis is that the toxicity of Cu and OTC mixture on physiological activity of fish was different from single OTC and Cu alone. The present study indicated that, compared to single OTC or Cu alone, Cu+OTC mixture reduced growth performance and feed utilization of grass carp, escalated the contents of Cu, OTC and TG, increased lipogenesis, induced oxidative stress, damaged the mitochondrial structure and functions and inhibited the lipolysis in the liver tissues and hepatocytes of grass carp. Cu+OTC co-treatment significantly increased the mRNA abundances and protein expression of Nrf2. Moreover, we found that Cu+OTC mixture-induced oxidative stress promoted Nrf2 recruitment to the SREBP-1 promoter and increased SREBP-1-mediated lipogenesis; Nrf2 sited at the crossroads of oxidative stress and lipid metabolism, and mediated the regulation of oxidative stress and lipid metabolism. Our findings clearly indicated that OTC and Cu mixture differed in environmental risks from single antibiotic or metal element itself, and thus posed different toxicological responses to aquatic animals. Moreover, our findings suggested that Nrf2 functioned as an important antioxidant regulator linking oxidative stress to lipogenic metabolism, and thus elucidated a novel regulatory mechanism for lipid metabolism.
Show more [+] Less [-]Pharmaceuticals, personal care products, food additive and pesticides in surface waters from three Australian east coast estuaries (Sydney, Yarra and Brisbane)
2020
Anim, Alfred K. | Thompson, Kristie | Duodu, Godfred O. | Tscharke, Ben | Birch, Gavin | Goonetilleke, Ashantha | Ayoko, G. A. (Godwin A.) | Mueller, Jochen F.
The detection rates of pharmaceuticals (Ps), personal care products (PCPs), current-use pesticides (CUPs) and a food additive (FA) in Brisbane River estuary (Queensland), Sydney estuary (New South Wales) and the Yarra River estuary (Melbourne, Victoria) were: Ps: 16/25, 7/25 and 12/25, respectively, CUPs; 28/53, 5/53 and 23/53, respectively, PCPs: 1/3, 0/3 and, 1/3, respectively and FA; 1/1, 1/1 and 1/1, respectively. Diuron was measured in all estuarine samples, simazine, MCPA and 2,4 D were also commonly measured. Pharmaceuticals: carbamazepine, iopromide paracetamol tramadol and venlafaxine were also commonly measured across the estuaries. Generally, analytes were prominent in Brisbane River estuary, followed by Yarra River/Sydney estuary. Inputs of Ps are likely from leakages or effluents of WWTPs; CUPs are potentially from agricultural and parklands via surface run-off in Brisbane River estuary, while for Sydney and Yarra estuaries, which have separate stormwater and sewer systems, sources are likely to be ingression and leakage.
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