PEST MANAGEMENT SCIENCE
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2020
·Vol. 76
·期 12
·4036-4045
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IF 3.75
Yifan Li,Hong Sun,Zhen Tian,Xinxin Su,Yue Li,Xuan Ye,Yifei Zhou,Shengli Zheng,Jiyuan Liu,Yalin Zhang
BACKGROUND Insect glutathione S-transferases (GSTs) play a crucial role in insecticide detoxification. However, there remains a distinct lack of information regarding the role of GSTs in the detoxification of Tolfenpyrad (TFP) in insects. RESULTS Real-time quantitative PCR showed significant upregulation of PxGSTs after exposure to TFP for 6 h. An in vitro inhibition assay showed that TFP could inhibit PxGSTδ, PxGSTε and PxGSTσ, and the most pronounced inhibitory effect was on PxGSTσ. Metabolism assays displayed that PxGSTσ was superior to other test PxGSTs in metabolizing TFP. The molecular docking of TFP and PxGSTσ revealed that the H-bond provided by the sidechains of Tyr107 and Tyr162 were key to the detoxification of TFP by PxGSTσ. Further tests using mutant PxGSTσ proteins at the sites of Tyr107 (PxGSTσY107A) and Tyr162 (PxGSTσY162A) corroborated that the individual replacement of Tyr107 and Tyr162 could greatly weaken the binding and metabolic abilities to TFP. CONCLUSION Metabolic interactions between the Plutella xylostella (L.) GSTs (PxGSTs) and TFP were deciphered. This study illustrates the molecular metabolism mechanism of PxGSTσ towards TFP and provides theoretical underpinnings for the design and optimization of novel TFP-like insecticides. © 2020 Society of Chemical Industry
研究领域:
昆虫学
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分子生物学
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农药科学
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PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2019
·Vol. 75
·期 7
·2009-2019
·
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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PubMed
高影响因子
ARCHIVES OF TOXICOLOGY
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2026
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IF 10.9
Deng Li,Yan Hanwen,Qian Zhipeng,Zhong Jiaqi,Xie Wenpei,Wang Jianfeng,Xu Jun,Gao Hong,Zong Liang,Chen Xijing,Huang Haoyan,Zhang Yongjie
Chlorfenapyr (CFP) is a halogenated pyrrole insecticide that requires metabolic activation to exert toxicity and has been associated with severe poisoning in humans. However, the metabolic pathways underlying CFP bioactivation and detoxification in humans remain poorly defined. In this study, we systematically investigated the metabolic fate of CFP and its toxic metabolite tralopyril (TLP) using in vitro human drug-metabolizing enzyme systems. Screening of ten human cytochrome P450 (CYP) isoforms at 5 and 50 µM CFP indicated that CYP2B6 is the major contributor to CFP bioactivation, which was further supported by selective inhibition and correlation analyses. CFP metabolism by CYP2B6 followed Michaelis–Menten kinetics, with showing a K m of 1.80 ± 0.57 μM, a V max of 0.24 ± 0.02 pmol/min/pmol P450, and an CL int of 139.78 ± 33.70 nL/min/pmol P450. In addition, incubations using 50 or 100 µM TLP and varying concentrations of glutathione (0.1 to 1 mM GSH) showed the formation of a novel GSH conjugate of TLP (TLP-GSH), of which level was markedly enhanced by human glutathione S-transferases (GSTs). Among six recombinant human GST isoforms tested, GSTA1, GSTA2, GSTM1, and GSTP1 showed significant catalytic activity in TLP-GSH formation compared with non-enzymatic reactions. Moreover, extracellular flux analysis revealed that TLP dose-dependently inhibited basal and maximal oxygen consumption rates, an effect exacerbated by GST inhibition, indicating a protective role of GSTs in TLP-induced mitochondrial toxicity. Together, these findings delineated metabolic enzymes-mediated bioactivation and detoxification pathways governing CFP toxicity in humans and provided a new perspective on clinical management strategies for CFP poisoning.
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高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 30
·期 15
·42587-42595
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IF 5.19
Yu Haikuo,Yang Xianmei,Dai Jinghua,Li Yuning,Veeran Sethuraman,Lin Jintian,Shu Benshui
The fall armyworm, Spodoptera frugiperda, has become a worldwide pest and threatens world food production. A previous study indicated that azadirachtin, the most effective botanical insecticide for S. frugiperda , inhibits larval growth of the insect. The effect of azadirachtin on the tissues of the larvae, however, remains to be determined. In this study, the effects of azadirachtin on the structure of fat bodies were analyzed. Comparative transcriptomic analysis was conducted between controls and samples treated with 0.1 μg/g azadirachtin for 7 days to explore potential relevant mechanisms. The expression of 5356 genes was significantly affected after azadirachtin treatment, with 3020 up-regulated and 2336 down-regulated. Among them, 137 encode detoxification enzymes, including 53 P450s , 20 GSTs , 27 CarEs , 16 UGTs , and 12 ABC transporters . Our results indicated that azadirachtin could destroy fat body structure and change the mRNA levels of detoxification-related genes. The up-regulated genes encoding detoxification enzymes might be related to detoxifying azadirachtin. Our results elucidate a preliminary mechanism of azadirachtin detoxification in the fat bodies of S. frugiperda larvae.
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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PubMed
高影响因子
Frontiers in Physiology
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2020
·
IF 3.367
Gao Haiming,Dai Lulu,Fu Danyang,Sun Yaya,Chen Hui
The Chinese white pine beetle (Dendroctonus armandi) is undoubtedly one of the most important pests causing ecological damage in the Qinling Mountains. When bark beetles invade conifers, they must overcome host tree defenses, including primary resistance and induced resistance responses. Moreover, this induced resistance occurs following herbivory by bark beetles. Bark beetles have a corresponding defense mechanism for degrading toxic compounds, and glutathione S-transferases (GSTs) can catalyze the binding of endogenous substances that reduce glutathione (GSH) to various harmful electrophilic substrates, increasing their solubility and facilitating their excretion from cells. In this experiment, we successfully obtained sixteen full-length sequences of D. armandi, which belonged to four GST categories (delta, epsilon, sigma, and theta). The transcript levels of sixteen GSTs in D. armandi were compared at four developmental stages (larvae, pupae, teneral adults, and adults), three different tissues (antennae, gut, and reproductive organs), and under various levels of terpenoid stimuli during feeding on phloem tissue to evaluate the various relevant modes of action. This study aids in the understanding of the interaction between monoterpenes and beetles, and beetles’ detoxification through GSTs.
研究领域:
昆虫学
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分子生物学
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生态毒理学
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PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
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IF 4
Ruosheng Yang,Hongle Xu,Qinghao Liu,Lanlan Sun,Wangcang Su,Fei Xue,Renhai Wu
Pyroxasulfone has been widely used to control malignant weeds in wheat fields. However, differences in pyroxasulfone tolerance across wheat varieties warrant attention owing to their potential impact on food production security. In this study, 54 wheat varieties were collected for screening, and Yunong 922 with 6.01-fold higher tolerance than Zhengmai 1354 was identified. Ultra-performance liquid chromatography–mass spectrometry analysis revealed that Yunong 922 exhibited a significantly shorter degradation half-life of pyroxasulfone (5.03 days) than Zhengmai 1354 (7.02 days). The P450 inhibitor malathion and the glutathione S-transferase (GST) inhibitor NBD-Cl reduced the tolerance factor of Yunong 922 to pyroxasulfone from 6.01 to 1.44 and 1.16, respectively, with no significant difference in tolerance to pyroxasulfone compared with Zhengmai 1354. RNA-Seq transcriptome analysis was used to identify candidate genes that may confer metabolic tolerance to pyroxasulfone in wheat. Eight candidate genes (five P450 enzymes and three GSTs) exhibited significantly different expression levels between Yunong 922 and Zhengmai 1354, as validated by qRT–PCR. Pyroxasulfone tolerance in Yunong 922 is associated with the coordinated upregulation of CYP72A397 , CYP72A14 , and GSTDHAR1 , each contributing approximately 33.7 %, 32.6 %, and 33.7 % to the dominant principal component 1 that accounts for 88.7 % of the explained variance. These results revealed that the faster degradation of pyroxasulfone observed in Yunong 922 could be linked to the higher expression of P450s and GSTs, though this relationship remains to be confirmed. This study also offers valuable insights into mechanisms underlying crop tolerance and informs the development of herbicide management strategies.
研究领域:
植物学
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作物科学
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农业科学
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分子生物学
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遗传学
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生物化学
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PubMed
高影响因子
Comparative Biochemistry and Physiology D-Genomics & Proteomics
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2019
·
IF 2.573
Xiao-rui Zhang,Jia-qi Zhang,Ying-ying Shao,Xiao-rong Xing,Jiao Wang,Zhi-xiang Liu,Yi-jiangcheng Li,Andrews Danso Ofori,Qing-bo Tu,Jun Wang,Sheng Sheng,Fu-an Wu
Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae) is a preponderant endoparasitoid wasp, attacking the larvae of many lepidopteran pests. We present the first body transcriptome dataset for M. pulchricornis . In total, 50,781,796 clean reads were obtained and 33,144 unigenes were assembled; 15,458 unigenes showed a significant similarity (E value < 10 −5 ) to known proteins in the NCBI non-redundant protein database . Gene ontology and cluster of orthologous group analyses were performed to classify the functions of genes. To better understand the role of glutathione-S-transferases (GSTs) in detoxification mechanism in M. pulchricornis , we identified seventeen GST genes ( MpulGSTs ) from the body transcriptome. Among these, fifteen MpulGSTs belonged to cytosolic GSTs and the other two belonged to microsomal classes. The cytosolic GSTs were classified into four different clades: four in delta, three in omega, seven in sigma, and one in zeta. The expression levels of these MpulGSTs after exposure to sub-lethal concentrations of phoxim and cypermethrin were determined using real-time quantitative polymerase chain reaction: seven MpulGSTs ( MpulGSTD3 , MpulGSTS1 , MpulGSTS2 , MpulGSTS4 , MpulGSTS6 MpulGSTO3 , and MpulGSTmic1 ) and 11 MpulGSTs ( MpulGSTD1 , MpulGSTD2 , MpulGSTD3 , MpulGSTO2 , MpulGSTS1 , MpulGSTS2 , MpulGSTS3 , MpulGSTS4 , MpulGSTS5 , MpulGSTS7 , and MpulGSTmic1 ) were highly expressed, respectively. These results suggested that GST genes may play a pivotal role in detoxification process in M. pulchricornis . Our findings would provide a theoretical base for elucidating insecticide susceptibility and should promote functional research on specific GST genes in parasitoid wasps.
研究领域:
昆虫学
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基因组学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Bochui Zhao,Xian Xu,Binghua Li,Zhizun Qi,Jinan Huang,Ali Hu,Guiqi Wang,Xiaomin Liu
Digitaria sanguinalis is a competitive and annual grass weed that commonly infests crops across the world. In recent years, the control of D. sanguinalis by nicosulfuron has declined in Hebei Province, China. To determine the resistance mechanisms of D. sanguinalis to nicosulfuron, a population of D. sanguinalis where nicosulfuron had failed was collected from a maize field of Hebei Province, China. Whole-plant dose–response experiments demonstrated that the resistant population (HBMT-15) displayed 6.9-fold resistance to nicosulfuron compared with the susceptible population (HBMT-5). Addition of the glutathione S-transferase (GSTs) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) significantly reduced the resistance level of the HBMT-15 population to nicosulfuron, and the GSTs activity of the HBMT-15 population was higher than the HBMT-5 population after nicosulfuron treatment. In vitro acetolactate synthase (ALS) enzyme experiments revealed that the nicosulfuron I 50 value for the HBMT-15 population was 41 times higher than that of the HBMT-5 population. An Asp 376 to Glu substitution in the ALS gene was identified in the HBMT-15 population. The HBMT-15 population had a moderate (2- to 4-fold) level of cross-resistance to three other ALS inhibitors (imazethapyr, pyroxsulam, and flucarbazone‑sodium), but was susceptible to pyrithiobac‑sodium. This study demonstrated that both an Asp 376 to Glu substitution in the ALS gene and GSTs-involved metabolic resistance to ALS inhibitors coexisted in a D. sanguinalis population .
研究领域:
植物学
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杂草科学
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植物生理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
·
IF 6.1
Chao Hu,Yu-Xi Liu,Shi-Pang Zhang,Ya-Qi Wang,Ping Gao,Yu-Ting Li,Xue-Qing Yang
Aryl hydrocarbon receptor (AhR) enhances insect resistance to insecticides by regulating the detoxification network. Our previous studies have confirmed that overexpressions of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are involved in lambda-cyhalothrin resistance in Cydia pomonella. Here, we report that CpAhR regulates the expression of GST and P450 genes, thus conferring resistance. Expression patterns indicated that the expression of CpAhR was highly induced by lambda-cyhalothrin exposure and upregulated in a lambda-cyhalothrin-resistant population. RNA interference (RNAi) of CpAhR decreases the expression of key resistance-related genes (CpGSTe3, CpCYP9A121, and CpCYP9A122) and the activity of the GST enzyme, reducing the tolerance to lambda-cyhalothrin. Furthermore, β-naphthoflavone, a novel agonist of AhR, was first proven to be effective in increasing CpAhR expression and larval tolerance to lambda-cyhalothrin. These results demonstrate that CpAhR regulates the expression of key detoxifying genes and GST activity, resulting in the development of resistance to lambda-cyhalothrin in C. pomonella.
研究领域:
昆虫学
·
分子生物学
·
毒理学
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PubMed
高影响因子
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