ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Fei Li,Lin Di,Yuxin Liu,Qiuyun Xiao,Xiaoyu Zhang,Fuying Ma,Hongbo Yu
Although ascomycetes occupy a vaster niche in soil than the well-studied basidiomycetes , they have received limited attention in studies related to bioremediation. In this study, the degradation of carbaryl by Xylaria sp. was studied in different culture conditions and its possible metabolic pathway was elucidated. In liquid culture, 99% of the added carbaryl was eliminated when cytochrome P450 (CYP450) was active, which was similar to the degradation rate of Pleurotus ostreatus , a fungus with strong bioremediation ability. Mn 2+ is beneficial to the degradation of carbaryl. Compared to the 72.17% degradation rate in sterile soil, 59.0% carbaryl was eliminated in non-sterile soil, which suggested that Xylaria sp. BNL1 can resist microorganismal infection. Furthermore, the intracellular fractions containing laccase, CYP450, and carbaryl esterase efficiently degraded carbaryl. The presence of carbaryl metabolites suggested that Xylaria sp. BNL1 initiated its attack on carbaryl via carbaryl esterase to release α-naphthol, which was further degraded to 1,4-naphthoquinone and benzoic acid by CYP450 and laccase. Thus, our study highlights the potential of using Xylaria sp. for bioremediation.
研究领域:
环境科学
·
微生物学
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PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
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2025
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IF 2.2
Min Li,Dongjie Wang,Xiaoping Huang,Shulan Wang,Zhenhan Chen,Muhammad Junaid,Shaolin Xie
Cyp1a (cytochrome P450 1 A) is critical for metabolizing endogenous substances and environmental chemicals. In this study, a zebrafish strain KI ( cyp1a:mcherry ), exhibiting low cyp1a gene expression, was compared with wild-type zebrafish (WT) to investigate the effects of cyp1a on growth and hypoxia tolerance. The results demonstrated that low cyp1a expression significantly inhibited zebrafish growth and reduced hypoxia tolerance. Specifically, KI zebrafish exhibited slower growth rates and higher sensitivity to low oxygen conditions compared to WT. These physiological phenotypes directly link low cyp1a expression to impaired growth and reduced environmental adaptation. Transcriptomic analysis revealed potential mechanisms underlying these effects, including up-regulation of digestive system-related genes (e.g., cpa1 , cpb1 ) and dysregulation of pathways involved in detoxification, stress response, and steroid biosynthesis. These findings highlight the importance of maintaining normal cyp1a expression for healthy growth and environmental adaptation in zebrafish.
研究领域:
分子生物学
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环境科学
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PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-14
·
IF 4.259
Lu Jian,Shao Yanjiao,Qin Xuan,Liu Daozhi,Chen Ang,Li Dali,Liu Mingyao,Wang Xin
Cytochrome P450 (CYP) 3A accounts for nearly 30% of the total CYP enzymes in the human liver and participates in the metabolism of over 50% of clinical drugs. Moreover, CYP3A plays an important role in chemical metabolism, toxicity, and carcinogenicity. New animal models are needed to investigate CYP3A functions, especially for drug metabolism. In this report, Cyp3a1/2 double knockout (KO) rats were generated by CRISPR-Cas9 technology, and then were characterized for viability and physiological status. The Cyp3a1/2 double KO rats were viable and fertile, and had no obvious physiological abnormities. Compared with the wild-type (WT) rat, Cyp3a1/2 expression was completely absent in the liver of the KO rat. In vitro and in vivo metabolic studies of the CYP3A1/2 substrates indicated that CYP3A1/2 was functionally inactive in double KO rats. The Cyp3a1/2 double KO rat model was successfully generated and characterized. The Cyp3a1/2 KO rats are a novel rodent animal model that will be a powerful tool for the study of the physiological and pharmacological roles of CYP3A, especially in drug and chemical metabolism in vivo .
研究领域:
药理学
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遗传学
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毒理学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2026
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IF 4.8
Yu-Ze Li,Chao Hu,Yu-Xi Liu,Yun-Tong Lv,Xue-Qing Yang
Extensive studies have demonstrated that cytochrome P450 enzymes play a critical role in the metabolic detoxification and resistance development of pests against insecticides; however, relative to P450 genes in Clan 3, knowledge on mitochondrial Clan members remains limited. Here, we report the involvement of a CYP333 family member, CYP333B119v2 , in conferring lambda -cyhalothrin resistance in Cydia pomonella . Phylogenetic analysis shows that CYP333B119v2 clusters with CYP333 family members of Lepidoptera, it containing three highly conserved P450 domains: the Heme-binding region, C-Helix, and K-helix. Spatiotemporal expression profiling indicates that CYP333B119v2 transcription levels increase progressively during larval development, peaking at the fourth instar, with significant expression in the midgut, the primary detoxification tissue. Relative to susceptible population (SS), CYP333B119v2 expression is 2.73-fold higher in lambda -cyhalothrin moderate resistant population (LCR) and is significantly induced by sublethal doses of lambda -cyhalothrin . Knockdown of CYP333B119v2 enhances larval susceptibility to lambda -cyhalothrin. Molecular docking based on AlphaFold models revealed strong binding interactions between CYP333B119v2 and lambda -cyhalothrin, with diverse non-covalent interactions involved in the binding process. These findings suggest that CYP333B119v2 may contribute to lambda -cyhalothrin resistance in C. pomonella . This study is the first report implicating a mitochondrial CYP333B subfamily member in the resistance mechanisms of Lepidoptera, advancing our understanding of P450-mediated metabolic resistance and providing new insights into pest management strategies.
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高影响因子
npj Science of Food
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2024
·Vol. 8
·期 1
·1-12
·
IF 6.3
Zhang Meng,Du Pengfei,Xiao Yirong,Liu Hao,Wang Meixue,Zhang Yumei,Chen Xin
Sodium dehydroacetate (DHA-Na), a widely used preservative, can induce sex-differentiated coagulation disorders primarily resulting from its metabolism. However, the underlying mechanisms remain poorly understood. Here, we identified several Cytochrome P450 (CYP450) sub-enzymes involved in sex differences related to DHA-Na metabolism, along with two related DHA-Na metabolites. CYP1A2, CYP3A2, and CYP2D1 were primarily responsible for DHA-Na metabolism, which was stronger in male rats than in female rats. Inhibition of these isoforms separately resulted in the DHA-Na metabolic capacity in male rats becoming equal to, or even weaker than, that in female rats. Furthermore, Cyp1a2, Cyp3a2, Cyp2d1 , and Cyp2c11 expression was higher in male rats than in female rats, suggesting these enzymes are related to exhibited sex differences in DHA-Na metabolism. Moreover, 3-glycoloyl-6-methy-2,3-dihydropyran-2,4-dione (C 8 H 8 O 5 ) and 3-imino-6-methyl-2,3-dihydropran-2,4dione (C 6 H 5 O 3 N) were identified as the two main DHA-Na metabolites. These findings provide crucial insights into potential mechanisms underlying sex differences in DHA-Na metabolism and its metabolites in rats.
研究领域:
药理学
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毒理学
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生物化学
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DOI
PubMed
高影响因子
Natural Product Communications
·
2019
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IF 0.554
Keling Cheng,Xuan Zeng,Hao Wu,Weiwei Su,Weiyang Fan,Yang Bai,Hongliang Yao,Peibo Li
Naringin (NRG) is a common dietary flavonoid in citrus fruits and has been documented to possess multiple pharmacological activities, including anti-oxidant, anti-inflammatory, and neuroprotective effects. Naringin is frequently consumed in combination with common clinical drugs. To date, the effects of NRG on cytochrome P450 enzymes have not been fully investigated yet. In this study, the activities of hepatic CYP1A2, CYP2D2, CYP2C9, CYP2C19, and CYP2E1 in rats after the continuous oral administration of NRG (50 and 500 mg/kg) were evaluated using cocktail probe-drug method. The concentrations of 5 probe drugs (phenacetin, dextromethorphan, diclofenac sodium, omeprazole, and chlorzoxazone) in rat plasma were simultaneously determined with a validated HPLC-MS/MS (high performance liquid chromatography-tandem mass spectrometry) method and then used to calculate corresponding pharmacokinetic parameters. Compared with the control group, the AUC(0-t), AUC(0-∞), t 1/2, and C max of each probe drug in treatment groups showed no significant differences. Meanwhile, fluorescence quantitative polymerase chain reaction (FQ-PCR) analysis revealed that NRG did not significantly affect the mRNA expressions of genes CYP1a2, CYP2d2, CYP2c6, CYP2c11, and CYP2e1 in rat liver. Based on these results, it could be concluded that NRG showed no significant effects on the activities and mRNA expressions of tested CYP450 in rats.
研究领域:
药理学
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分子生物学
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DOI
高影响因子
CHEMOSPHERE
·
2023
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IF 8.8
Xiaoyuan Guo,Lan Qiu,Zhiwei Liang,Qihong Lu,Shanquan Wang,Hojae Shim
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased the demand of disinfectant use. Chloroxylenol ( para -chloro- meta -xylenol, PCMX) as the major antimicrobial ingredient of disinfectant has been widely detected in water environments, with identified toxicity and potential risk. The assessment of PCMX in domestic wastewater of Macau Special Administrative Region (SAR) showed a positive correlation between PCMX concentration and population density. An indigenous PCMX degrader, identified as Rhodococcus sp. GG1, was isolated and found capable of completely degrading PCMX (50 mg L −1 ) within 36 h. The growth kinetics followed Haldane's inhibition model, with maximum specific growth rate, half-saturation constant, and inhibition constant of 0.38 h −1 , 7.64 mg L −1 , and 68.08 mg L −1 , respectively. The degradation performance was enhanced by optimizing culture conditions, while the presence of additional carbon source stimulated strain GG1 to alleviate inhibition from high concentrations of PCMX. In addition, strain GG1 showed good environmental adaptability, degrading PCMX efficiently in different environmental aqueous matrices. A potential degradation pathway was identified, with 2,6-dimethylhydroquinone as a major intermediate metabolite. Cytochrome P450 (CYP450) was found to play a key role in dechlorinating PCMX via hydroxylation and also catalyzed the hydroxylated dechlorination of other halo-phenolic contaminants through co-metabolism. This study characterizes an aerobic bacterial pure culture capable of degrading PCMX metabolically, which could be promising in effective bioremediation of PCMX-contaminated sites and in treatment of PCMX-containing waste streams.
研究领域:
环境科学
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微生物学
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DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
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2016
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IF 1.651
Lulu Dai,Mingyuan Ma,Guanqun Gao,Hui Chen
Bark beetles oxidize the defensive allelochemicals of their host trees both to detoxify them and convert them into components of their pheromone systems which were catalyzed by cytochrome P450 enzymes (CYPs) and occur in different tissues of the insect. We study P450 genes in the Chinese white pine beetle ( Dendroctonus armandi ), and some bio-information analysis was done for the full-length deduced amino acid sequences. The tissue specificity of these P450 genes was determined in three tissues (antenna, gut and reproductive organs). Differential expression of the P450 genes was observed between sexes, and within these significant differences exposed to stimuli (α-pinene (1:1 racemic mix), (S)-(−)-α-pinene, (S)-(−)-β-pinene, (+)-3-carene, (±)-limonene and turpentine oil) at 24 h. Increased expression of P450 genes suggested that they play a role in the detoxification of monoterpenes released by the host trees. The different transcript accumulation patterns of these bark beetle P450 genes provided insight into ecological interactions of D . armandi with its host pine.
研究领域:
昆虫学
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分子生物学
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生态学
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生物信息学
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DOI
PubMed
高影响因子
JOURNAL OF PEST SCIENCE
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2025
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IF 4.1
Lin Kai,Wu Hongxin,Li Zhongsheng,Zhong Zichun,He Liuyan,Guo Yujing,Zhang Jie,Xu Xiaoxia,Zhang Wenqing,Jin Fengliang,Pang Rui
Insecticide resistance in pest control poses a threat to agricultural production and human health. Numerous insect species express genes coding for detoxification enzymes that have broad substrate promiscuity thus conferring resistance to various insecticides. However, whether the homologs of these genes play similar roles in resistance phenotypes of closely related species remains largely unclear. Therefore, this study compares the resistance profiles of three major rice planthopper species (Delphacidae) ( Laodelphax striatellus , Nilaparvata lugens , and Sogatella furcifera ) based on the metabolic activity of their cytochrome P450s. Genome-wide analyses resulted in 68, 70, and 64 P450 genes in L. striatellus , N. lugens , and S. furcifera , respectively. Phylogenetic analyses among these genes found that most resistance-related genes in one species had homologs in other planthopper species. The most resistance-relevant orthogroup ( CYP6ER s) showed higher evolutionary instability than most other groups. RNAi and in vitro metabolism assays revealed that CYP6ER s confers more divergent insecticide resistance profiles among planthopper species than the other two major resistance-related P450 subfamilies ( CYP6AY s and CYP4C61 s). Alphafold-based structural predictions and alignments suggested that P450 orthogroups with higher phylogenetic instability tended to have less structural similarities, resulting in more divergent metabolic profiles. This relationship was also in silico validated on Aphidae aphids and Lepidoptera noctuids. This study proposes combined phylogenetic and toxicogenomic analyses for understanding CYPome-based insecticide resistance convergency and divergency among closely related pests. These findings may improve the accuracy and rationality of chemical pest control.
研究领域:
昆虫学
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毒理学
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基因组学
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DOI
高影响因子
XENOBIOTICA
·
2017
·
IF 1.932
Hui Li,Dongju Lin,Ying Peng,Jiang Zheng
1. Nitrofurantoin (NFT), a 5-nitrofuran derivative, has been widely used for the treatment of specific urinary tract infections. It has been reported that exposure to NFT was associated with various adverse effects, particularly hepatotoxicity and pneumotoxicity. The objective of the study was to identify reactive metabolites of NFT and explore the mechanisms of the toxicities.2. An epoxide intermediate generated in microsomal incubations was trapped by glutathione (GSH) and 4-bromobenzyl mercaptan (BBM), and the resulting GSH and BBM conjugates were characterized by LC–MS/MS. A spontaneous denitration took place in the trapping reaction. 2-Nitrofuran and 2-hydroxyfuran as model compounds were employed to probe the mechanism of the denitration.3. The oxidative activation of NFT was P450-dependent, and P450 3A5 and P450 2A6 were the principal enzymes responsible for the bioactivation. The findings facilitate the understanding of the mechanisms of NFT-induced toxicities.
研究领域:
药理学
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毒理学
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DOI
PubMed
高影响因子
Marine Drugs
·
2021
·Vol. 19
·期 2
·63
·
IF 5.118
Guo-Fang Duan,Yang Liu,Li-Na Zhang,Hong-Ye Li,Jie-Sheng Liu,Wei-Dong Yang
Diarrhetic shellfish toxins (DSTs), some of the most important phycotoxins, are distributed almost all over the world, posing a great threat to human health through the food chain. Therefore, it is of great significance to find effective methods to reduce toxin accumulation in shellfish. In this paper, we observed the effects of four phytochemicals including cinnamaldehyde (CA), quercetin, oridonin and allicin on the accumulation of DSTs in the digestive gland ofPerna viridisafter exposure to the DSTs-producingProrocentrum lima. We found that, among the four phytochemicals, CA could effectively decrease the accumulation of DSTs (okadaic acid-eq) in the digestive gland ofP. viridis. Further evidence demonstrated that CA could reduce the histological alterations of the digestive gland of a mussel caused by DSTs. RT-qPCR showed that CA could suppress the CYP3A4 induction by DSTs, suggesting that the DSTs’ decrease induced by CA might be related to the inhibition of CYP3A4 transcription induction. However, further studies on the underlying mechanism, optimal treatment time, ecological safety and cost should be addressed before cinnamaldehyde is used to decrease the accumulation of DSTs in field.Keywords:okadaic acid;Perna viridis;cinnamaldehyde;CYP3A4
研究领域:
海洋生物学
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毒理学
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药理学
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PubMed
高影响因子
Chilean Journal of Agricultural Research
·
2017
·Vol. 77
·期 3
·257-265
·
IF 0.719
Wei Li,Lele Zhang,Ning Zhao,Wenlei Guo,Weitang Liu,Lingxu Li,Jinxin Wang
ABSTRACT American slough grass ( Beckmannia syzigachne (Steud.( Fernald) is a worldwide weed and is widely distributed in rice-wheat rotations in China. Fenoxaprop- P -ethyl and mesosulfuron-methyl are two major herbicides used to control B. syzigachne . Resistance has evolved in B. syzigachne under continuous selective pressure from herbicides. This study aimed to establish the cross-resistance pattern of a resistant population and explore the potential non-target-site based resistance mechanisms of B. syzigachne . Sequencing of target enzyme genes (acetyl coenzyme A carboxylase (ACCase( and acetolactate synthase (ALS() revealed that there were no resistance-endowing amino acid substitutions in the resistant B. syzigachne population (R F1 ) compared with the sensitive population (S F1 ), and obtained the purified materials. Furthermore, piperonyl butoxide (PBO) and malathion showed synergistic effects with fenoxaprop- P -ethyl and mesosulfuron-methyl respectively in R F1 . Therefore, we speculate that the resistance observed in B. syzigachne was related with metabolic, mostly involving the cytochrome P450 enzymes. Cross resistance patterns showed that the purified resistant B. syzigachne produce high resistance to fenoxaprop- P -ethyl and pyroxsulam; intermediate resistance to flucarbazone-sodium; low resistance to quizalofop- P -ethyl, clodinafop-propargyl, sethoxydim and mesosulfuron-methyl; sensitive to clethodim pinoxaden and isoproturon. Key words: Herbicide resistance; metabolic resistance; P450 inhibitors; target enzymes sequencing.
研究领域:
植物学
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分子生物学
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农业科学
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PubMed
高影响因子
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