PEST MANAGEMENT SCIENCE
·
2019
·Vol. 75
·期 7
·2009-2019
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IF 3.255
Bo Hu,He Huang,Qi Wei,Miaomiao Ren,David K Mburu,Xiangrui Tian,Jianya Su
BACKGROUND Glutathione S -transferases (GSTs) are a superfamily of multifunctional dimeric proteins existing in both prokaryotic and eukaryotic organisms. They are involved in the detoxification of both endogenous and exogenous electrophiles, including insecticides. However, the molecular mechanisms underlying the regulation of GST genes in insects are poorly understood. RESULTS We first identified at least three GST genes involved in resistance to the insecticides chlorpyrifos and cypermethrin. Analysis of upstream sequences revealed that three GSTs ( SeGSTo2 , SeGSTe6 and SeGSTd3 ) harbor the same cap ‘n’ collar C/muscle aponeurosis fibromatosis (CncC/Maf) binding site, and SeGSTo2 and SeGSTe6 contain the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) binding site. Luciferase reporter assay showed co-transfection of reporter plasmid containing the SeGSTe6 promoter with CncC and/or Maf expressing constructs significantly boosted transcription. Similarly, AhR and/or ARNT expressing constructs also significantly increased the promoter activities. The co-transfection of mutated reporter plasmid with CncC/Maf or AhR/ARNT did not increase transcription activity anymore. Constitutive over-expression of CncC, Maf and AhR was also found in the HZ16 strain, which might be the molecular mechanism for up-regulated expression of multiple detoxification genes conferring resistance to insecticides. CONCLUSION These results suggest that CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GST genes involved in insecticide resistance in Spodoptera exigua . © 2019 Society of Chemical Industry
研究领域:
昆虫学
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分子生物学
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毒理学
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基因组学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2025
·
IF 3.5
Yongjun Tang,Zhengning Feng,Chenlu Ma,Nian Jang,Xiaolong Chen,Yingxu He,Francis L. Martin,Hui Liu,Weiyi Pang
Breast cancer has a high global incidence, and benzo[ a ]pyrene (B[ a ]P) is considered a contributing factor that increases carcinogenic risk. This study examined B[ a ]P's oncogenic mechanisms in mammary epithelial cells. Chronic B[ a ]P exposure induced morphological changes and enhanced proliferative/clonogenic capacity in MCF-10A cells. Chronic B[ a ]P exposure altered gene expression in MCF-10A cells, revealing differential levels of circRNAs, lncRNAs, miRNAs, and mRNAs. qRT-PCR validation demonstrated strong alignment with RNA-seq results, ensuring sequencing reliability. Additionally, chronic B[ a ]P exposure upregulated the protein expression of AhR and ARNT, as well as TGF- β , pSmad2/3, and KRT14 , while increasing Vimentin expression and decreasing E-cadherin expression. Notably, treatment with the TGF- β inhibitor SB431542 reversed these protein expression changes in transformed cells. These results show that exposure to Chronic B[ a ]P induces MCF-10A cell transformation. The underlying mechanisms involve significant transcriptional alterations, AhR/ARNT expression regulation, TGF- β signaling pathway activation, KRT14 protein modulation, and EMT. Furthermore, Chronic B[ a ]P exposure may drive transformation through TGF- β modulation. Chronic B[ a ]P exposure promotes breast carcinogenesis, revealing mechanistic insights and potential preventive biomarkers.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cells
·
2022
·Vol. 11
·期 23
·3856
·
IF 7.666
Bin Liu,Hui Chen
The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) belong to the bHLH-PAS (basic Helix–Loop–Helix–Period/ARNT/Single-minded) family of transcription factors, which participate in the sensing and transmitting stimuli of exogenous and endogenous chemical substances, and subsequently activates genes transcription involved in various detoxification and physiological functions. However, they have not been identified inDendroctonus armandi,and their roles in the detoxification metabolism are unclear. In the present study,AhRandARNTofD. armandiwere characterized. Spatiotemporal expression profiling indicated thatDaAhRandDaARNTwere highly expressed in the adult and larval stages ofD. armandiand mainly expressed in the midgut and Malpighian tubules of adults. Additionally, the expression ofDaAhRandDaARNTsignificantly increased after exposure to (−)-?-pinene, (+)-3-carene, and (±)-limonene. SilencingDaAhRandDaARNTincreased the susceptibility ofD. armandito (−)-?-pinene, (+)-3-carene, and (±)-limonene, and the activities of detoxification enzyme were also remarkably reduced. Moreover,DaCYP6DF1andDaGSTs2were significantly down-regulated after injections ofdsAhRanddsARNTin the male and female adults, with the expression ofDaCYP6DF1decreasing by higher than 70%. The present study revealed that the transcription factorsAhRandARNTofD. armandiwere induced by terpenoids and participated in the regulation ofDaCYP6DF1 expression, which was associated withD. armandi’s susceptibility to (−)-?-pinene and (±)-limonene. These results may provide a theoretical basis for the integrated control ofD. armandiand improve our comprehension of insect toxicology.Keywords:Dendroctonus armandi;AhR;ARNT;detoxification metabolism;transcriptional regulation
研究领域:
昆虫学
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分子生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Anxiang Zhuang,Xu Zhao,Xiaoxue Lu,Shengyi Wang,Xi Zeng,Xiaoyu Li,Siquan Yu,Meiqi Xie,Yang Mei,Haibin Yuan,Xiangkun Meng
BACKGROUND The aryl hydrocarbon receptor (AhR) and its dimerization partner ARNT are well-established regulators of xenobiotic metabolism in vertebrates, but their functional roles in insect detoxification remain poorly characterized. This study investigates the involvement of TcAhR/TcARNT in the detoxification of insecticides and plant allelochemicals in the red flour beetle, Tribolium castaneum . RESULTS We found that the expressions of TcAhR and TcARNT were significantly induced upon exposure to imidacloprid, deltamethrin, or (−)-4-terpineol. RNA interference (RNAi)-mediated silencing of TcAhR and TcARNT dramatically increased larval susceptibility to these chemicals, and concurrently suppressed the activities of key detoxification enzymes, including P450s, CarEs, GSTs and UGTs. Conversely, treatment with the AhR agonist β-naphthoflavone upregulated TcAhR / TcARNT expression, enhanced detoxification enzyme activities, and decreased chemical susceptibility. Transcriptome analysis following TcAhR / TcARNT knockdown identified 34 co-regulated detoxification enzyme genes, the vast majority of which were downregulated. Among these, TcFE4 and TcUGT2B7 were functionally validated to be critical for detoxification, as their individual silencing significantly heightened larval chemical susceptibility. Furthermore, bioinformatic analysis revealed that 32 co-regulated genes contained potential AhR/ARNT binding motifs in their promoters, and several were physically clustered and consistently downregulated on chromosomes. CONCLUSION These results demonstrate that the TcAhR/TcARNT pathway plays a central role in regulating a battery of detoxification genes in T. castaneum , thereby modulating its tolerance to synthetic insecticides and plant allelochemicals. This study provides fundamental insights into the molecular mechanisms of insect detoxification and resistance. © 2025 Society of Chemical Industry.
研究领域:
毒理学
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分子生物学
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昆虫学
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遗传学
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农药科学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Juanjuan Duan,Hong Li,Yu Wang,Yongchao Ji,Chao Chen,Chengqiang Feng,Wensheng Zhang
Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant which mainly exposed though diet. High-fat diet (HFD) can induce atherosclerosis, as can BaP. Unhealthy dietary habits lead to high intake of both BaP and lipids. However, the combined effect of BaP and HFD on atherosclerosis and lipid accumulation in the arterial wall, the initial stage of atherosclerosis, is unclear. In this study, C57BL/6 J mice were subchronically exposed to BaP and a HFD, and the mechanism of lipid accumulation was investigated in EA.hy926 and HEK293 cells. Results showed that BaP and HFD increased blood lipids and damaged aortic wall synergistically. Meanwhile, LDL enhanced the toxicity of BaP, and BaP promoted the production of reactive oxygen species and malonaldehyde in EA.hy926 cells, which aggravated LDL-induced cell injury. Moreover, BaP and HFD/LDL induced LDL accumulation in the aortic wall of C57BL/6 J mice/EA.hy926, and the mechanism was by activating AHR/ARNT heterodimer to combine with the scavenger receptor BⅠ (SR-BⅠ) and activin receptor-like kinase 1 (ALK1) promoter regions to transcriptional upregulate its expression, which enhanced the uptake of LDL, and promoting the production of AGEs to inhibit reverse cholesterol transport by SR-BI. BaP and lipid synergistically promoted aortic and endothelial damage, and the health risk of their combined intake should be paid attention to.
研究领域:
毒理学
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心血管疾病
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环境健康
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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