INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 25
·期 18
·10188
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IF 4.9
Peng Zhao,Zifu Wang,Shimei Liao,Yangxin Liao,Shijun Hu,Jianchun Qin,Donghua Zhang,Xiaohui Yan
Salvia leucanthais a perennial herb of the genusSalviain the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action ofS. leucanthaon Alzheimer’s disease (AD), the anti-AD activity of SLE (extracts ofS. leucantha) was determined by using a transgenicCaenorhabditis elegans(C. elegans) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (S. leucanthapetroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity ofC. elegansN2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment inC. elegans,mainly involving longevity regulatory pathways—nematodes, drug metabolism—cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the genegst-5; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components inS. leucanthamay serve as new-type anti-AD candidates and provide some insights into their biological functions.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2024
·
IF 2.9
Shaojie Wu,Kuofei Liao,Jiamin Chen,feng li
Although chlorambucil (CHL) is a long-established anticancer drug, the drug failure of CHL, mediated by the intracellular defense system consisting of glutathione (GSH) and glutathione S-transferase pi (GST-pi), has significantly limited the application of CHL. To overcome this issue, we first designed a GSH-responsive small-molecule prodrug (EA-SS-CHL) by combining CHL and ethacrynic acid (EA). Subsequently, drug-loaded nanoparticles (ECPP) were formed by the self-assembly between EA-SS-CHL and amphiphilic PEG-PDLLA to improve the water solubility of the prodrug and its ability to target tumor sites. Upon exposure to high intracellular GSH concentration, EA-SS-CHL gradually degrades, leading to the release of EA and CHL. The presence of EA facilitates the depletion of GSH and inhibition of GST-pi, ultimately attenuating the detoxification of the intracellular defense system to CHL. Cytotoxicity studies and apoptosis assays demonstrate that ECPP exhibits higher therapeutic efficiency than CHL. Additionally, in vivo tumor suppression effects and biocompatibility provide further evidence for the superiority of ECPP. This work presents a promising strategy to enhance the efficacy of CHL in cancer therapy.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Qiyi Zhu,Xiaofeng Zhu,Ning Yang,Yuxi Duan,Yuanyuan Wang,Xiaoyu Liu,Di Zhao,Haiyan Fan,Lijie Chen
Root-knot nematodes ( Meloidogyne incognita ) present a significant threat to global agriculture, and the development of multi-drug resistance in these nematodes exacerbates this problem. Benzothiazole, a heterocyclic compound has been reported as a potential nematicide, however, its mode of action is not fully understood. This study aims to elucidate the nematicidal mechanism of benzothiazole against M. incognita . In the toxicity assays, benzothiazole exhibited rapid and effective nematocidal activity, significantly compromising egg masses and inhibiting egg hatching while killing newly hatched second-stage juveniles (J2s) of M. incognita . Microscopic observations revealed that after 48 h of incubation, a marked reduction in protein and carbohydrate levels within the J2s was observed. Notably, benzothiazole at a concentration of 14 mmol/L significantly inhibits glutathione S-transferase (GST) enzyme activity, leading to the accumulation of reactive oxygen species (ROS), ultimately resulting in rapid nematode death. Molecular docking and dynamics simulations demonstrated that benzothiazole forms a stable complex with GST, thereby disrupting its antioxidant function. Furthermore, in pot experiments, benzothiazole effectively reduced the gall formations of M. incognita on tomato roots. Overall, this novel inhibitory mechanism of glutathione S-transferase (GST) differs from that of the neurotoxicant abamectin, which targets glutamate-gated chloride channels (GluCl). This mechanism holds significant promise for the development of environmentally friendly nematicides. It offers a potential solution to the growing problem of multidrug resistance in root-knot nematodes and could help mitigate the substantial economic losses caused by these pests in global agriculture.
研究领域:
农业科学
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害虫防治
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生物化学
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线虫学
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植物病理学
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DOI
PubMed
高影响因子
Nanomaterials
·
2015
·Vol. 5
·期 4
·1571-1587
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IF 2.076
Bing Han,Yanli Wang,Lan Wang,Zuhui Shang,Shuang Wang,Jin Pei
During the chemotherapy of cancer, drug resistance is the first issue that chemotherapeutic drugs cannot be effectively used for the treatment of cancers repeatedly for a long term, and the main reason for this is that tumor cell detoxification is mediated by GSH (glutathione) catalyzed by GST (glutathione-S-transferase). In this study, a GST inhibitor, ethacrynic acid (ECA), was designed to be coupled with methoxy poly(ethylene glycol)-poly(lactide) (MPEG–PLA) by disulfide bonds to prepare methoxy poly(ethylene glycol)-poly(lactide)-disulphide bond-mthacrynic acid (MPEG–PLA–SS–ECA) as a carrier material of the nanoparticles. Nanoparticles of pingyangmycin (PYM) and carboplatin (CBP) were prepared, respectively, and their physicochemical properties were investigated. The ECA at the disulfide could be released in the presence of GSH, the pingyangmycin, carboplatin and ECA were all uniformly released, and the nanoparticles could release all the drugs completely within 10 days. The half maximal inhibitory concentration (IC50) of the prepared MPEG–PLA–SS–ECA/CBP and MPEG–PLA–SS–ECA/PYM nanoparticles in drug-resistant oral squamous cell carcinoma cell lines SCC15/CBP and SCC15/PYM cells was 12.68 μg·mL−1and 12.76 μg·mL−1, respectively; the resistant factor RF of them in the drug-resistant cells were 1.51 and 1.24, respectively, indicating that MPEG–PLA–SS–ECA nanoparticles can reverse the drug resistance of these two drug-resistant cells.Keywords:nanoparticle;GST inhibitor;redox-sensitive;self-assembly
研究领域:
药学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
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2018
·Vol. 69
·期 10
·2595-2608
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IF 5.354
Luo Huifeng,Dai Cheng,Li Yongping,Feng Jia,Liu Zhongchi,Kang Chunying
The red color of the foliage and fruit in strawberry comes from anthocyanins stored in the vacuole; however, how this anthocyanin accumulation is regulated remains unclear. A reduced anthocyanin in petioles (rap) mutant was identified in an N-ethyl-N-nitrosourea (ENU) mutagenized population of YW5AF7, a white-fruited variety of the wild strawberry Fragaria vesca. The causative mutation was identified to be a premature stop codon in a glutathione S-transferase (GST) gene. In addition to the foliage coloration, RAP also mediates fruit pigmentation and acts downstream of the fruit-specific transcription factor FvMYB10. Among all eight GST genes in the same subfamily, RAP is most abundantly expressed in the ripening fruit. Expression analysis and transient expression assays demonstrated that RAP is the principal transporter of anthocyanins among the paralogs. Moreover, domain-swap experiments showed that both the N- and C-terminals of RAP are essential for the binding capability of anthocyanins. In addition, transient knock-down of RAP resulted in reduced fruit coloration in cultivated strawberry. Collectively, our results demonstrate that RAP encodes the principal GST transporter of anthocyanins in the strawberry foliage and fruit, and it could be modified to alter the fruit color in strawberry.
研究领域:
植物学
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遗传学
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分子生物学
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DOI
PubMed
高影响因子
NanoImpact
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2021
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IF 5.316
Wanjun Zhang,Jinling Gao,Lin Lu,Tsendmaa Bold,Xin Li,Shuo Wang,Zhishang Chang,Jing Chen,Xiao Kong,Yuxin Zheng,Mingliang Zhang,Jinglong Tang
Glutathione (GSH) and glutathione-S-transferases (GSTs) are two frontlines of cellular defense against both acute and chronic toxicity of xenobiotics-induced oxidative stress. The contribution of GSH and GST enzymes to signaling pathways and the regulation of GSH homeostasis play a central role in the detoxification of numerous environmental toxins and impurities. Iron oxide nanoparticles stemmed from traffic exhaust, steel manufacturing, or welding as a potential environmental pollution can lead to adverse respiratory outcomes and aggravate the risk of chronic health conditions via persistent oxidative stress. In this work, two kinds of acute exposure experiments of iron oxide (Fe 2 O 3 and Fe 3 O 4 ) nanoparticles in cells and in vivo were conducted to evaluate the GSH levels and GST activity. Our current research presented Fe 3 O 4 nanoparticles at lower concentrations (≤100 μg/ml) seem to be more toxic to the human bronchial epithelial cells as their consumption of GSH and decrease of GST activity. The catalysis activity of Fe 3 O 4 nanoparticles per se may contribute to the intracellular GSH consumption along with inhibition of glutathione-S-transferase class mu 1 and P (GSTM1 and GSTP1) active site and expression decrease of GSTM1 and GSTP1. Accordingly, the GSH consumption and decrease in GST activity directed to the further lipid peroxidation regarded as an earlier marker for toxicity evaluation of iron oxide nanoparticles, and relevant intervention may be effective for prevention of respiratory exposure induced damage from iron oxide nanoparticles.
研究领域:
毒理学
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纳米技术
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2015
·Vol. 72
·期 4
·816-827
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IF 2.694
Lulu Dai,Junning Ma,Mingyuan Ma,Haoqiang Zhang,Qi Shi,Ranran Zhang,Hui Chen
BACKGROUND Bark beetles rely on their detoxifying enzymes to resist the defensive terpenoids of host trees. Glutathione S -transferases (GSTs) conjugate xenobiotic compounds with a glutathione moiety (GSH) and often work in tandem with cytochromes P450 or other enzymes that aid in the detoxification, sequestration or excretion of toxic compounds. RESULT We identified nine new GST genes in the Chinese white pine beetle ( Dendroctonus armandi ) and carried out a bioinformatics analysis on the deduced full-length amino acid sequences. These genes belong to four different classes (epsilon, sigma, omega and theta). Differential transcript levels of each class of GST genes were observed between sexes, and, within these levels, significant differences were found among the different adult substages that were fed phloem of Pinus armandi and exposed to six stimuli [(±)- α -pinene, (−)- α -pinene, (−)- β -pinene, (+)-3-carene, (±)-limonene and turpentine] at 8 and 24 h. CONCLUSION The increased transcription levels of GST genes suggested that they have some relationship with the detoxification of terpenoids that are released by host trees. The mediating oxidative stress that is caused by monoterpene might be the main role of the bark beetle GSTs. © 2015 Society of Chemical Industry
研究领域:
昆虫学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yu-Ting Li,Jia-Lu Pei,Tong Huan,Yue Wu,Ye-Wang Zhang
Although heparinase II has been widely used in the structural analysis of heparin and HS, it suffers from low activity and inefficient expression and purification. In this study, heparinase II from Mariniphaga anaerophila ( Ma HepII) was cloned, and the GST tag was fused to the backside of the enzyme's active pocket. The fusion protein GST- Ma HepII was efficiently expressed in the recombinant Escherichia coli BL21. Afterward, Ni-NTA affinity chromatography was used to purify GST- Ma HepII, with an enzymatic activity recovery yield of 70.3 % and a specific activity of 7.5 U mg −1 toward heparin. When HS was used as the substrate, the enzyme exhibited a specific activity of 11.1 U mg −1 . Additionally, the influence of the GST tag on the enzymatic properties of Ma HepII was evaluated. After removal of the GST tag by proteolytic cleavage, Ma HepII was purified by GSH affinity chromatography. Characterization of the enzymatic properties indicated that the GST tag improved the catalytic efficiency of Ma HepII by 3.1-fold toward heparin and 1.4-fold toward HS. Molecular docking revealed that the GST tag fusion might increase the flexibility of the protein structure and alter the size or shape of the substrate channel. These changes facilitate substrate access to the active site and enhance the catalytic efficiency of Ma HepII.
研究领域:
酶工程
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分子生物学
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蛋白质表达与纯化
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结构生物学
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生物催化
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Liting Zhang,Xiaoxin Yan,Ting Jiang,Jie Han,Jianqiang Xiao,Kai Wang,Donglin Hao,Rui Guo,Jianhua Jin
This study introduces Hcy-GST, a new dual-modal optical probe for detecting glutathione S-transferase (GST) activity. The probe combines hemicyanine and rhodamine derivatives, which use fluorescence and photoacoustic (PA) signals, controlled by a photoinduced electron transfer (PET) mechanism. In its original form, the nitro groups in Hcy-GST quench fluorescence, producing weak fluorescence and strong PA signals. When GST replaces the nitro groups with glutathione (GSH), the PET effect is interrupted, leading to fluorescence recovery and reduced PA signals. Hcy-GST shows high sensitivity, with fluorescence and PA signals strongly correlating with GST concentration. It has high selectivity and minimal interference from other substances. In cellular tests, Hcy-GST detected GST inhibition by ethacrynic acid. In vivo studies revealed lower GST activity in obese models, with PA signals increasing after probe injection. Hcy-GST demonstrated excellent stability and low toxicity, showing promise for GST detection in research and diagnostics.
研究领域:
生物化学
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医学诊断
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DOI
高影响因子
ACS Sensors
·
2025
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IF 9.1
Kai Wang,Jia-Wei Li,Rui Guo,Rong Hu,Zhao-Cheng Liu,Hao-Xiang Jiang
Detecting glutathione S-transferases (GSTs) in cardiovascular diseases is crucial for understanding oxidative stress and its role in disease progression, but it remains challenging due to GST’s dynamic expression and interactions with other cellular components. In this study, the CS-GST optical probe was developed to monitor GST activity. The probe demonstrated unique optical properties, with fluorescence intensity increasing and photoacoustic signals decreasing upon interacting with GST. It showed excellent sensitivity and selectivity, with strong correlations between fluorescence and GST concentration. In cellular and in vivo experiments, CS-GST effectively tracked GST activity in foam cell models and mice, showing potential as a biomarker for cardiovascular diseases. Overall, CS-GST is a highly sensitive, selective, and stable tool with promising applications in cardiovascular disease research, offering a noninvasive method for real-time monitoring of GST activity.
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DOI
PubMed
高影响因子
JOURNAL OF ASIA-PACIFIC ENTOMOLOGY
·
2024
·
IF 1.1
Qing-Hua Xiao,Wu-Ye Li,Jin Zhang,Jia-Min Yu,Dong-Yang Liu,Jiang-Nan Peng,Mao-Ye Li,Su Liu
In insects, the transcription factor cap ‘n’ collar isoform C (CncC) plays a critical role in the regulation of multiple genes involved in insecticide detoxification. Knockdown of CncC genes leads to increased susceptibility to different types of insecticides in several insect species. However, the CncC gene has not yet been fully characterized in the black cutworm Agrotis ipsilon , a notorious insect pest that causes severe damage to field crops. In this study, the CncC gene (designated AiCncC ) was identified from A. ipsilon . Exposure to a median lethal concentration (LC 50 ) of chlorantraniliprole (CAP) or phoxim (PHO) strongly increased the expression of AiCncC . Silencing of AiCncC by RNA interference significantly increased the susceptibility of A. ipsilon larvae to both insecticides. Moreover, CncC/Maf binding sites were predicted in the putative promoters of two glutathione S -transferase (GST) genes ( AiGSTe1 and AiGSTu1 ) involved in the detoxification of CAP and PHO. The transcription levels of AiGSTe1 and AiGSTu1 were dramatically decreased by silencing AiCncC . These findings indicate that AiCncC is associated with CAP and PHO susceptibility through the regulation of GST genes.
研究领域:
昆虫学
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分子生物学
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害虫防治
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DOI
高影响因子
Journal of Toxicologic Pathology
·
2019
·
IF 1.153
Qian Tang,Mei Zhang,Zexuan Hong,Yao Chen,Pan Wang,Jian Wang,Zili Wang,Rendong Fang,Meilan Jin
To clarify the suppressive effects of astragalus injection (AI) on different stages of early hepatocarcinogenesis induced by weak promotion, SD rats initiated with a single intraperitoneal (i.p.) injection of N-diethylnitrosamine (DEN) at 200 mg/kg body weight and promoted with 0.5% piperonyl butoxide (PBO) in diet were repeatedly administered AI at 5 ml/kg body weight/day in the early postinitiation (EPI) or late postinitiation (LPI) period for 2 or 8 weeks, respectively. The number and area of glutathione S-transferase placental form (GST-P)-immunoreactive (+) foci tended to increase in the DEN+PBO group compared with the DEN-alone group. Among the PBO-promoted groups, number and area of GST-P+ foci did not visibly change in the DEN+PBO+AI-EPI group compared with the DEN+PBO group. In contrast, number and area of GST-P+ foci tended to decrease in the DEN+PBO+AI-LPI group compared with the DEN+PBO group. Number of Ki67+ cells was increased in the DEN+PBO group compared with the DEN-alone group and was decreased in both AI-administered groups compared with the DEN+PBO group. Gene expression analysis revealed that the DEN+PBO+AI-LPI group showed increased transcript levels of Ccne1, Cdkn1b, Rb1, Bax, Bcl2, Casp3, and Casp9 compared with the DEN+PBO group; however, the DEN+PBO+AI-EPI group did not show changes in the transcript levels of any genes examined compared with the DEN+PBO. These results suggest that AI administration during the LPI period caused weak suppression of hepatocarcinogenesis under weak promotion with a low PBO dose by the mechanism involving facilitation of cell cycle suppression causing G1/S arrest and apoptosis via the mitochondrial pathway. In addition, the results suggest that AI administration during the EPI period has no effect on weakly promoted hepatocarcinogenesis.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）