MOLECULES
·
2023
·Vol. 28
·期 1
·340
·
IF 4.6
Jingqi Sun,Limin Jia,Xuwei Chen
Glutathione S-transferases (GSTs) are important type-II detoxification enzymes that protect DNA and proteins from damage and are often used as protein tags for the expression of fusion proteins. In the present work, octa-aminopropyl caged polyhedral oligomeric silsesquioxane (OA–POSS) was prepared via acid-catalyzed hydrolysis of 3-aminopropyltriethoxysilane and polymerized on the surface of graphene oxide (GO) through an amidation reaction. Glutathione (GSH) was then modified to GO–POSS through a Michael addition reaction to obtain a GSH-functionalized GO–POSS composite (GPG). The structure and characteristics of the as-prepared GPG composite were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravity analysis, and surface charge analysis. The specific binding interactions between glutathione and GST gave GPG favorable adsorption selectivity towards GST, and other proteins did not affect GST adsorption. The adsorption behavior of GST on the GPG composite conformed to the Langmuir isotherm model, and the adsorption capacity of GST was high up to 364.94 mg g−1under optimal conditions. The GPG-based solid-phase adsorption process was applied to the extraction of GST from a crude enzyme solution of pig liver, and high-purity GST was obtained via SDS-PAGE identification.Keywords:octa-aminopropyl caged polyhedral oligomeric silsesquioxane (OA–POSS);graphene oxide (GO);glutathione S-transferases (GST);adsorption;solid-phase extraction
研究领域:
生物化学
·
材料科学
·
酶学
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 4
·448
·
IF 4.8
Xueli Guo,Zhongyan Liu,Lina Wu,Pan Guo
Background : Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods : A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w / w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results : The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug ( p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls ( p < 0.001), leading to 58.7% tumor volume reduction ( p < 0.001). Conclusions : The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy.
研究领域:
药剂学
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肿瘤学
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DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2025
·
IF 15.4
Chen Zixiang,Niu Kaifeng,Li Mengge,Deng Yuchun,Zhang Ji,Wei Di,Wang Jiaqi,Zhao Yongliang
Tumor cells evolve strong antioxidant capacities to counteract the abnormal high level of reactive oxygen species (ROS) in the tumor microenvironment. Glutamate-cysteine ligase catalyzing subunit (GCLC) for synthesis of antioxidant glutathione (GSH) represents the key enzyme to maintain redox homeostasis of tumor cells, however, whether its activity is regulated by posttranslational modifications, such as succinylation, remains to be clarified. Here, we demonstrate the existence of succinylation modification on GCLC by in vitro and in vivo assays. NAD-dependent deacetylase Sirtuin-2 (SIRT2) serves as the desuccinylase and catalyzes GCLC desuccinylation at sites of K38, K126, and K326. Specifically, GCLC directly interacts with SIRT2, which can be substantially enhanced upon ROS treatment. This strengthened association results in GCLC desuccinylation and activation, consequently promoting GSH synthesis and rendering cancer cells resistant to ferroptosis induction. Depletion of SIRT2 decreases total GSH level and meanwhile increases the cellular susceptibility to ferroptosis, which can mostly be rescued by introducing wild-type GCLC, but not its 3K-E mutant. We further demonstrated that histone acetyltransferase P300 serves as the succinyltransferase of GCLC, and their association is remarkably decreased after ROS treatment. Thus, SIRT2-regulated GCLC succinylation represents an essential signaling axis for cancer cells to maintain their redox balance in coping with oxidative stress-induced ferroptosis.
研究领域:
肿瘤生物学
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细胞代谢
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2016
·
IF 4.712
Xi Dai,Zhi-Fang Du,Li-Hong Wang,Jun-Ying Miao,Bao-Xiang Zhao
We have designed and synthesized a simple but effective fluorescent probe for sensing glutathione (GSH) by PET process based on coumarin and quinone , which worked as fluorophore and reaction site, respectively. The probe could discriminate GSH from cysteine and homocysteine within 1 min in PBS-buffered solution. The sensing mechanism was confirmed by density functional theory (DFT), viscosity test, fluorescence spectrum analysis and HRMS , respectively. The probe has a low limit of detection (0.1 μM) and finally been used in cell imaging successfully.
研究领域:
生物化学
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分析化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Hui-Yun Zhang,Cong-yong Sun,Michael Adu-Frimpong,Jiang-nan Yu,Xi-ming Xu
The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 6
·1639-1649
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IF 4.157
Fereja Shemsu Ligani,Fang Zhongying,Li Ping,Guo Jinhan,Fereja Tadesse Haile,Chen Wei
Balanced level of hemin in the body is fundamentally important for normal human organ function. Therefore, environmentally benign, stable, and fluorescent metal nanoclusters (NCs) for selective and sensitive detection of hemin have been investigated and reported. Herein, highly orange red emissive gold NCs are successfully synthesized using glutathione as a reducing and stabilizing agent (GSH-Au NCs). The clusters are characterized using various techniques like Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), UV-vis spectroscopy, and fluorescence spectrometer. The fluorescence intensity of as-synthesized Au NCs strongly quenched upon addition of different concentrations of hemin. The decrease in fluorescence intensity of GSH-Au NCs has been applied for determination of hemin concentration in the linear range from 1 to 25 nM with a low limit of detection (LOD) of 0.43 nM. The method was also successfully applied for quantification of hemin in human serum sample. In view of this reality, the system can be considered as a possible strategy and excellent platform for determination of hemin in various areas of application. Graphical abstract
研究领域:
生物化学
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医学检测
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纳米技术
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DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 72
·45792-45798
·
IF 3.108
Huili Ye,Hao Wang,Faqiong Zhao,Baizhao Zeng
A stable graphene (GR)/CdS:Mn photocatalyst was synthesized through a simple and straightforward one-pot hydrothermal method, and it exhibited enhanced photoelectrochemical (PEC) response to glutathione. The catalyst was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and UV-vis diffuse reflectance spectroscopy. It showed efficient separation of photogenerated charge carriers and low photo-corrosion. The doped Mn2+ effectively improved the band structure of CdS. Meanwhile, the introduced GR greatly enhanced and facilitated visible light absorption as well as electron transport. The GR/CdS:Mn based PEC sensor displayed more sensitive photocurrent response to glutathione than the pure CdS, CdS:Mn and GR/CdS based sensors. Furthermore, the response of the sensor was rapid and stable. The details of the additions and specific effects of each component were discussed. Under the optimized conditions, it presented wide detection range of 0.01 μM to 100 μM, low detection limit, as well as good reproducibility. The sensor could be applied to the determination of glutathione in tomato and ketchup samples.
研究领域:
材料科学
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分析化学
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DOI
高影响因子
Agriculture-Basel
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2022
·Vol. 12
·期 10
·1528
·
IF 3.408
Shengnan Li,Zedong Wu,Chunhong Liu,Lianxue Fan,Yongheng He,Ke Lu,Dajun Liu,Guojun Feng
Propamocarb is a pesticide widely used to control cucumber downy mildew. The overuse of propamocarb has resulted in residues and phytotoxicity. However, the detoxification and metabolic process of propamocarb have not been documented well. Our previous work showed differences in the propamocarb residues among the different genotypes of cucumber and their regulation by multiple genes. Based on the already reported data on gene expression profiles under propamocarb treatment, we identified the glutathione pathway, including six different genes (Csa4M303130,Csa3M133380,Csa5M409710,Csa7M395820,Csa3M597320, andCsa1M571280), involved in propamocarb detoxification. The qPCR analysis showed thatCsa1M571280(CsGSH2) was most significantly and differentially expressed at 48 h after propamocarb spray in the cucumber varieties Y3F604 (low propamocarb residues) and M729 (high propamocarb residues). In Y3F604,CsGSH2expression increased from 6 to 48 h after spraying propamocarb, and the expression was positively correlated with propamocarb residues, whereas M729 showed no significant difference inCsGSH2expression. Therefore, we presumedCsGSH2as a key gene in managing propamocarb residues. Gene functional analysis showed that propamocarb residues decreased inCsGSH2-overexpressing plants and increased inCsGSH2-antisense plants. Overexpression ofCsGSH2enhanced glutathione (GSH) accumulation and glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPX) activities, probably for propamocarb detoxification. The activity of antioxidant enzymes (SOD, POD, CAT, and APX) increased to maintain a high antioxidant capacity inCsGSH2-overexpressing plants. The superoxide (O2−), hydrogen peroxide (H2O2), and malondialdehyde (MDA) levels decreased inCsGSH2-overexpressing plants, promoting the antioxidant system composed of ascorbic acid and glutathione (AsA-GSH). Thus, we conclude thatCsGSH2alleviates propamocarb residues and phytotoxicity by enhancing cucumber’s antioxidant and glutathione detoxification potential.Keywords:cucumber;propamocarb;antioxidant;glutathione;detoxification
研究领域:
植物科学
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分子生物学
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农业化学
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DOI
高影响因子
Foods
·
2023
·Vol. 12
·期 10
·1931
·
IF 5.2
Dashan Guo,Yuwei Hou,Hongshan Liang,Lingyu Han,Bin Li,Bin Zhou
The distinctive assembly behaviors of lysozyme (Lys) feature prominently in food, materials, biomedicine, and other fields and have intrigued many scholars. Although our previous work suggested that reduced glutathione (GSH) could induce lysozyme to form interfacial films at the air/water interface, the underlying mechanism is still obscure. In the present study, the effects of GSH on the disulfide bond and protein conformation of lysozyme were investigated by fluorescence spectroscopy, circular dichroism spectroscopy, and infrared spectroscopy. The findings demonstrated that GSH was able to break the disulfide bond in lysozyme molecules through the sulfhydryl/disulfide bond exchange reaction, thereby unraveling the lysozyme. The β-sheet structure of lysozyme expanded significantly, while the contents of α-helix and β-turn decreased. Furthermore, the interfacial tension and morphology analysis supported that the unfolded lysozyme tended to arrange macroscopic interfacial films at the air/water interface. It was found that pH and GSH concentrations had an impact on the aforementioned processes, with higher pH or GSH levels having a positive effect. This paper on the exploration of the mechanism of GSH-induced lysozyme interface assembly and the development of lysozyme-based green coatings has better instructive significance.Keywords:reduced glutathione;lysozyme;defolding;self-assembly
研究领域:
食品科学
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材料科学
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生物医学
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DOI
PubMed
高影响因子
Analytical Methods
·
2022
·Vol. 14
·期 48
·5034-5040
·
IF 3.532
Guoli Wu,Yongdan Zhao,Xiaofang Li,Xiaolin Lu,Tingli Qu
Glutathione (GSH) is a polypeptide with important physiological functions. Real-time and accurate detection of GSH is of great significance for clinical diagnosis, disease treatment and pathogen detection. A fluorescent nanosensor based on composite core–shell nanoparticles for the highly selective detection of GSH is reported. In the cores, the fluorescence of rhodamine b was quenched by using gold nanoparticles (AuNPs), and GSH could competitively combine with AuNPs to cause rhodamine b to fall off, thereby recovering the fluorescence. In the shell part, molecularly imprinted materials using oxidized glutathione (GSSG) as a pseudotemplate provide GSH/GSSG specific pores and improve the specificity and anti-interference ability of the sensor. The GSH sensor has a detection range of 0–100 μM and limit of detection (LOD) of 0.18 μM, and robust sensing performance in fetal bovine serum, indicating its great potential for clinical diagnosis.
研究领域:
分析化学
·
纳米技术
·
生物医学工程
·
临床诊断
✓ 已验证
DOI
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Nho Soo Bin,Do Sang-Hun,Oh Seongjin,Park Yong-Cheol,Kim Sun-Ki
This study aimed to develop a non-genetically modified organism (non-GMO) Saccharomyces cerevisiae strain with enhanced glutathione production using UV-induced random mutagenesis. Among 30 wild-type strains, S. cerevisiae KACC 48331 was selected for its high glutathione production. A #14 mutant with significantly higher glutathione content was isolated via acrolein resistance screening. Optimal batch fermentation was established at 20 °C and pH 4.5 using a cost-effective medium of molasses and corn steep liquor (CSL). In fed-batch fermentation, the #14 mutant achieved 1.98 g/L of glutathione using molasses and CSL as carbon and nitrogen sources, comparable to yields from expensive complex media containing peptone and yeast extract. Notably, over 99% of the glutathione produced was in the reduced, biologically active form. These results demonstrate the feasibility of using non-GMO yeast and industrial by-products for sustainable and economical glutathione production.
研究领域:
生物技术
·
微生物发酵
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工业微生物学
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代谢工程
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应用微生物学
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产品关联
DOI
PubMed
高影响因子
Methods and Applications in Fluorescence
·
2019
·Vol. 7
·期 3
·034004
·
IF 2.94
Nan Cao,Huangmei Zhou,Hao Tan,Ruijuan Qi,Jinquan Chen,Sanjun Zhang,Jianhua Xu
In this work, we report a sensitive and selective turn-on fluorescence detection of cysteine with glutathione protected silver nanoclusters (GSH-Ag NCs). The glutathione stabilized silver nanoclusters were synthesized by the boiling water method. When excited at 380 nm, the GSH-Ag NCs exhibited a weak emission at about 680 nm, which could be enhanced by cysteine. The proposed method allows evaluation of cysteine in the range of 2–3000 μM with a detection limit of 0.51 μM. The recoveries were found to be 95.07%-101.38% when detecting cysteine contents in fetal bovine serum samples. In addition, we also discussed the possible mechanism for the fluorescence enhancement of GSH-Ag NCs by addition of cysteine. It might be the formation of cysteine and glutathione co-capped Ag NCs. This work reported a fluorimetric method for the assay of cysteine and provided a strategy for the synthesis of dual ligand-protected Ag nanoclusters.
研究领域:
分析化学
·
生物医学
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DOI
PubMed
高影响因子
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