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1.
J Sci Food Agric ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567792

RESUMO

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.

2.
Food Chem ; 442: 138615, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309242

RESUMO

Rice gluten, as the hydrophobic protein, exhibits restricted application value in hydrophilic food, which may be enhanced through interaction with soybean 11S globulin, characterized by favorable functional properties. This study aims at revealing their interaction mechanism via multi-spectroscopy and molecular dynamics simulation. The formation and structural change of rice glutelin-soybean 11S globulin complexes were detected using fluorescence, ultra-violet and circular dichroism spectra. The addition of 11S globulin increased the contents of α-helix, ß-turn and random coil, but decreased ß-sheet content, and the change in secondary structure was correlated with particle size. Moreover, exposure of hydrophobic groups and formation of disulfide bonds occurred in the complexes. Molecular dynamics simulation verified these experimental results through analyses of root mean square deviation and fluctuation, hydrogen bond, secondary structure, and binding free energy analysis. This study contributes to expounding the interaction mechanism of protein and protein from the molecular level.


Assuntos
Globulinas , Oryza , Glutens/química , Soja , Oryza/metabolismo , Simulação de Dinâmica Molecular , Espectrometria de Fluorescência , Globulinas/química , Simulação de Acoplamento Molecular
3.
J Sci Food Agric ; 104(4): 2484-2492, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37972116

RESUMO

BACKGROUND: It is well known that hemp proteins have the disadvantages of poor solubility and poor emulsification. To improve these shortcomings, an alkali covalent cross-linking method was used to prepare hemp protein isolate-epigallocatechin-3-gallate biopolymer (HPI-EGCG) and the effects of different heat treatment conditions on the structure and emulsifying properties of the HPI-EGCG covalent complex were studied. RESULTS: The secondary and tertiary structures, solubility, and emulsification ability of the HPI-EGCG complexes were evaluated using particle size, zeta potential, circular dichroism (CD), and fluorescence spectroscopy indices. The results showed that the absolute value of zeta potential of HPI-EGCG covalent complex was the largest, 18.6 mV, and the maximum binding amount of HPI to EGCG was 29.18 µmol g-1 . Under heat treatment at 25-35 °C, the α-helix content was reduced from 1.87% to 0%, and the ß-helix content was reduced from 82.79% to 0% after the covalent binding of HPI and EGCG. The solubility and emulsification properties of the HPI-EGCG covalent complexes were improved significantly, and the emulsification activity index (EAI) and emulsion stability index (ESI) were increased by 2.77-fold and 1.21-fold, respectively. CONCLUSION: A new HPI-EGCG covalent complex was developed in this study to provide a theoretical basis for the application of HPI-EGCG in food industry. © 2023 Society of Chemical Industry.


Assuntos
Cannabis , Catequina , Catequina/análogos & derivados , Cannabis/química , Calefação , Antioxidantes/química , Catequina/química , Biopolímeros
4.
Food Res Int ; 173(Pt 2): 113473, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803796

RESUMO

This study aimed to hydrolyze soy isolate protein (SPI) using five enzymes (alcalase, pepsin, trypsin, papain, and bromelain) in order to obtain five enzymatic hydrolysates and to elucidate the effect of enzymes on structural and biological activities of the resulting hydrolysates. The antioxidant and hypoglycemic activities of the soy protein isolate hydrolysates (SPIEHs) were evaluated through in silico analysis, revealing that the alcalase hydrolysate exhibited the highest potential, followed by the papain and bromelain hydrolysates. Subsequently, the degree of hydrolysis (DH), molecular weight distribution (MWD), amino acid composition, structure, antioxidant activities, and hypoglycemic activity in vitro of SPIEHs were analyzed. After enzymatic treatment, the particle size, polymer dispersity index (PDI), ζ-potentials, ß-sheet content and α-helix content of SPIEHs was decreased, and the maximum emission wavelength of all SPIEHs exhibited red-shifted, which all suggesting the structure of SPIEHs was unfolded. More total amino acids (TAAs), aromatic amino acids (AAAs), and hydrophobic amino acids (HAAs) were found in alcalase hydrolysate. For 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal ion chelating activity, α-glucosidase inhibitory activity and α-amylase inhibitory activity, alcalase hydrolysate had the lowest IC50; alcalase hydrolysate and papain hydrolysate had the lowest IC50 for hydroxyl radical scavenging activity. Physiological activity of SPIEHs was evaluated thoroughly by 5-Axe cobweb charts, and the results revealed that alcalase hydrolysate exhibited the greatest biological activities.


Assuntos
Antioxidantes , Bromelaínas , Antioxidantes/farmacologia , Antioxidantes/química , Papaína/química , Hidrolisados de Proteína/química , Proteínas de Soja , Aminoácidos , Subtilisinas/química
5.
J Food Sci ; 88(8): 3494-3506, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37326339

RESUMO

This study investigated the effects of extrusion on the physical properties of glutinous rice and addressed the challenges associated with its hardened texture and reduced taste in glutinous rice products by adding extruded glutinous rice to assess their anti-retrogradation effect compared with different improvers. Glutinous rice flour with different gelatinization degrees was obtained by changing the initial moisture content of glutinous rice grains before extrusion, and their physicochemical properties and the effect of adding them to rice products were analyzed. Results showed that with the increase in moisture content, the viscosity, water absorption index of extruded glutinous rice flour, and product viscosity increased, while the gelatinization degree, water solubility index, and product elasticity decreased, and the hardness of the rice products showed a trend of first decreasing and then increasing. Twenty percent moisture content of glutinous rice products showed the best properties mentioned above. The effects of adding different improvers on retrogradation degree, quality characteristics, microstructure, and moisture migration of glutinous rice products were analyzed by texture profile analysis, sensory evaluation, scanning electron microscopy, and low-field nuclear magnetic resonance. It was found that soybean polysaccharides, xanthan gum, and extruded glutinous rice flour had better anti-retrogradation effects, while colloid and soybean polysaccharides provided a tighter and more three-dimensional internal structure to the rice products. Our study showed that extruded glutinous rice flour had good anti-retrogradation properties and little effect on flavor and taste, but it would increase the roughness and viscosity of the products, which had advantages and disadvantages compared with other improvers.


Assuntos
Oryza , Oryza/química , Fenômenos Químicos , Viscosidade , Solubilidade , Água/química , Farinha/análise
6.
Front Nutr ; 10: 1122045, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342551

RESUMO

Postmenopausal osteoporosis is one of the most common metabolic diseases in old women, and supplementing estrogen through bioactive substances is one of the important ways to improve menopausal syndrome. Some studies have confirmed that soybean isoflavone has estrogenic activity, and the main active component of soybean isoflavones is isoflavone aglycones. However, few studies have investigated the improvement effect of high-purity soy isoflavone aglycones on postmenopausal osteoporosis. Thus, the effect of different doses of high-purity soybeans isoflavone aglycone on the ovariectomized female osteoporosis rat model was evaluated by oral gavage. The rats were divided into seven experimental groups including SHAM, OVX, EE, SIHP, AFDP-L, AFDP-M, and AFDP-H, which was administered for 60 days from 30 days after ovariectomy. We collected blood from the abdominal aorta of rats on the 30th, 60th, and 90th days respectively, analyzed its serum biochemistry, and took out the femur for micro-CT imaging and bone microstructure parameter analysis. Results showed that the intervention effect of AFDP-H group on osteoporosis rats at 60 and 90 days was similar to that of EE group, and superior to the OVX group, SIHP group, AFDP-L group, AFDP-M group. The AFDP-H group inhibited the decrease in serum bone markers, bone density, trabeculae quantity, trabeculae thickness, and bone volume fraction, and increased the trabecular separation caused by ovariectomy, thereby significantly improving bone microstructure. It also prevented continuous weight gain and increased cholesterol levels in female rats. This study provided theoretical to application of soybean isoflavone aglycone in the intervention of osteoporosis. and confirmed that could replace chemical synthetic estrogen drugs.

7.
J Sci Food Agric ; 103(13): 6566-6573, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37229570

RESUMO

BACKGROUND: This study used enzymatic and Ca2+ cross-linking methods to prepare edible soy protein isolate (SPI) and sodium alginate (SA) interpenetrating polymer network hydrogels to overcome the disadvantages of traditional interpenetrating polymer network (IPN) hydrogels, such as poor performance, high toxicity, and inedibility. The influence of changes in SPI and SA mass ratio on the performance of SPI-SA IPN hydrogels was investigated. RESULTS: Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were used to characterize the structure of the hydrogels. Texture profile analysis (TPA), rheological properties, swelling rate, and Cell Counting Kit-8 (CCK-8) were used to evaluate physical and chemical properties and safety. The results showed that, compared with SPI hydrogel, IPN hydrogels had better gel properties and structural stability. As the mass ratio of SPI-SA IPN changed from 1:0.2 to 1:1, the gel network structure of hydrogels also tended to be dense and uniform. The water retention and mechanical properties of these hydrogels, such as storage modulus (G'), loss modulus (G"), and gel hardness increased significantly and were greater than those of the SPI hydrogel. Cytotoxicity tests were also performed. The biocompatibility of these hydrogels was good. CONCLUSIONS: This study proposes a new method to prepare food-grade IPN hydrogels with mechanical properties of SPI and SA, which may have strong potential for the development of new foods. © 2023 Society of Chemical Industry.


Assuntos
Alginatos , Hidrogéis , Hidrogéis/química , Alginatos/química , Polímeros/química , Proteínas de Soja , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Food Funct ; 14(5): 2472-2480, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36799431

RESUMO

This study investigated the in vitro antibacterial activity of Lactobacillus acidophilus AD125 against Escherichia coli (E. coli) O157:H7 and its probiotic properties: gastrointestinal tolerance, surface hydrophobicity, autoaggregation, coaggregation, and adhesion to Caco-2 cells. In addition, the action mode of the strain's antagonism against adhesion of E. coli O157:H7 to Caco-2 cells was analyzed, and related substances were also determined. Results showed that L. acidophilus AD125 had stronger antibacterial activity (inhibition zone of 20.47 ± 0.43 for AD125 culture solution and 14.55 ± 1.12 for cell-free supernatant) against E. coli O157:H7 than other Lactobacillus spp. Also, this strain had higher gastrointestinal tolerance, autoaggregation percentage (26.51 ± 0.71%), and coaggregation percentage (23.97 ± 0.44%) with E. coli O157:H7. High surface hydrophobicity of toluene and xylene (83.59 ± 2.54% and 93.45 ± 1.24%) was also observed. Bacterial adhesion counts were 1176.54 100 per cells, indicating good adhesion to Caco-2 cells. Furthermore, the exclusion, competition, and antibacterial effect of AD125 may have driven its antagonism against E. coli O157:H7 adhesion. Finally, surface-layer proteins, extracellular polysaccharides, and thermosensitive substances all participated in the antagonism against E. coli O157:H7, with surface-layer proteins the main related substances. These results show that Lactobacillus acidophilus AD125 is promising for inhibiting E. coli O157:H7 and preventing and treating intestinal diseases induced by E. coli O157:H7.


Assuntos
Escherichia coli O157 , Probióticos , Humanos , Lactobacillus acidophilus , Células CACO-2 , Probióticos/farmacologia , Antibacterianos/farmacologia , Aderência Bacteriana
9.
J Sci Food Agric ; 103(1): 118-124, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35811466

RESUMO

BACKGROUND: Quinoa is a good gluten-free resource for food processing, especially bread making, and can improve and prevent the development of complications associated with celiac disease (CD). However, lack of gluten affects quinoa bread quality. Previous research showed that soy protein isolate (SPI) could improve gluten-free bread quality to some extent. Therefore, this study investigated the effects of SPI on the physical properties of quinoa dough and gluten-free bread quality characteristics. RESULTS: Results showed that, with appropriate SPI substitution, the farinograph properties of quinoa flour significantly improved (P < 0.05). The sample with 8% SPI substitution showed a better development time (DT, 3.30 ± 0.20 min), stability time (ST, 8.80 ± 0.10 min) and softening degree (SD, 8.80 ± 0.10 FU), which were close to those of wheat flour, although more water absorption (WA, 76.40 ± 2.10%) was needed than for wheat flour (66.30 ± 3.10%). The extensograph properties of quinoa flour also significantly improved after 8% SPI substitution (P < 0.05). Furthermore, SPI substitution increased G' moduli of quinoa dough and decreased tan δ to some extent, providing better rheological properties closer to those of wheat dough. SPI substitution also improved the quality and texture of quinoa bread and reduced the gap with wheat bread. When SPI substitution was 8%, the specific volume, hardness and springiness of quinoa bread were 2.29 ± 0.05 mL g-1 , 1496.47 ± 85.21 g and 0.71 ± 0.03%, respectively. CONCLUSION: These results suggested that SPI substitution would be an effective way to develop higher-quality gluten-free bread. © 2022 Society of Chemical Industry.


Assuntos
Pão , Chenopodium quinoa , Farinha , Proteínas de Soja/química , Triticum/química , Glutens/química
10.
Food Res Int ; 162(Pt B): 112108, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461408

RESUMO

Broken rice is an important by-product during milling process of rice, which is rich in protein. To increase the value of by-products and search for effective antioxidants, the antioxidant peptides from broken rice protein hydrolysate were separated and identified by ultrafiltration, gel filtration chromatography, fast protein liquid chromatography, and LC-MS/MS in this study. These identified peptides were further screened using a combined in silico and in vitro method and their antioxidant mechanism was explored by Western blot and molecular docking analysis. Ninety-eight peptides were obtained after antioxidant activity-oriented isolation and four novel peptides, SGDWSDIGGR, DFGSEILPR, GEPFPSDPKKQLQ, and GEKGGIPIGIGK, with excellent solubility, safety, and antioxidant activity were synthesized. Among these, SGDWSDIGGR showed good antioxidant activities in the extracellular assay (41.57 µmol TE/g and 29.41 % in ORAC and DPPH assay, respectively.), and it possessed a protective effect against H2O2-injured oxidative stress in 2BS cells in a dose-dependent manner. Furthermore, Western blot and molecular docking results showed that SGDWSDIGGR achieves antioxidant ability by occupying the Nrf2-binding site, activating the Keap1-Nrf2 signaling pathway, and upregulating the expression of antioxidant enzymes. This study extends the rice industry chain and provides insights into the selection and mechanisms research of antioxidant peptides.


Assuntos
Oryza , Hidrolisados de Proteína , Hidrolisados de Proteína/farmacologia , Antioxidantes/farmacologia , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch , Peróxido de Hidrogênio , Cromatografia Líquida , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Peptídeos/farmacologia
11.
Food Chem ; 390: 133210, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35580517

RESUMO

Covalent grafting of one of the two flavonols (kaemperol and quercetin) to caseinate was achieved by a reaction between the heat-oxidized flavonols and caseinate at flavonol-lysine molar ratios of 1:100 and 1:200. Grafted caseinate products (GCPs) showed - NH2 content reduction and respective kaemperol and quercetin contents of 1.08-6.13 and 3.23-6.64 mmol/kg protein. Quercetin was more reactive than kaemperol under the same conditions, while long-time flavonol heat and higher flavonol-lysine molar ratio caused greater flavonol-grafting. GCPs subjected to 180-day storage had further flavonol-grafting, -NH2 content decrease, and weak protein crosslinking. GCPs consistently had higher surface hydrophobicity but lower emulsification and digestibility than caseinate, while greater flavonol-grafting caused a remarkable value change. Meanwhile, the Kjeldahl method was more suitable than the UV-absorption method to evaluate protein digestibility, because the grafted flavonols in this case did not interfere with data results. Collectively, the covalent flavonol-grafting of proteins can impact the assayed protein functionalities.


Assuntos
Flavonóis , Quercetina , Caseínas , Flavonoides/metabolismo , Flavonóis/metabolismo , Lisina , Quercetina/metabolismo
12.
Chem Biol Interact ; 328: 109201, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717190

RESUMO

The caseinate and glycated caseinate generated from the transglutaminase-catalyzed reaction of caseinate and oligochitosan were digested using pepsin and trypsin, and the activity of the resultant digests was measured in rat intestinal epithelial cell line (IEC-6) using several biological responses as indicators. Compared with the caseinate digest, the glycated caseinate digest had similar contents in 17 amino acids but less reactable -NH2 contents, and 6.57 g glucosamine per kg protein; moreover, it showed higher activity in the cells (P < 0.05) to promote cell growth, accumulate the cell-cycle progression at the S-phase, and prevent the camptothecin-induced cell apoptosis. The glycated caseinate digest also showed higher differentiation activity in the cells than the caseinate digest, resulting in enhanced activities of the three brush-border membrane enzymes (P < 0.05) and increased microvilli on the cell surfaces. The real-time reverse transcription-polymerase chain reaction, Western-blot assay, and Dickkopf-1 (a receptor inhibitor of the Wnt/ß-catenin signaling pathway) were used to determine both gene and protein expression changes in the cells. A Wnt/ß-catenin signaling pathway responsible for these enhanced effects was proposed because the five genes (glycogen synthase kinase 3ß, Wnt3a, ß-catenin, c-Myc, and cyclin D1) and three proteins (nuclear and cytosolic ß-catenin, cyclin D1, and c-Myc) as part of this signaling pathway were regulated in the treated cells. The oligochitosan glycation of caseinate induced by transglutaminase is thus suggested endowing the peptic-tryptic caseinate digest with higher activity in the cells through its effects on the Wnt/ß-catenin signaling pathway.


Assuntos
Caseínas/metabolismo , Quitina/análogos & derivados , Enterócitos/metabolismo , Pepsina A/metabolismo , Tripsina/metabolismo , Via de Sinalização Wnt , Animais , Apoptose , Bovinos , Pontos de Checagem do Ciclo Celular , Diferenciação Celular/genética , Proliferação de Células , Sobrevivência Celular , Quitina/metabolismo , Quitosana , Enterócitos/citologia , Enterócitos/ultraestrutura , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosilação , Oligossacarídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
13.
Antioxidants (Basel) ; 8(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480571

RESUMO

Non-covalent interactions and in vitro radical scavenging activities of the complexes formed by the commercial milk protein product caseinate and one of the two polyphenols (galangin and genistein) were assessed by the multi-spectroscopic techniques, molecular docking, and detection of scavenging activities against the 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals. The caseinate bound with the two polyphenols showed conformational changes and increased scavenging activities, compared with original caseinate. The caseinate-polyphenol binding was driven by the hydrophobic interaction and hydrogen-bonds, while hydrophobic interaction was the main binding force. Meanwhile, sodium dodecyl sulfate and urea could damage the essential hydrophobic interaction and hydrogen-bonds, respectively, and thus led to decreased apparent binding constants for the caseinate-polyphenol binding. Based on the measured values of several apparent thermodynamic parameters like ΔH, ΔS, ΔG, and donor-acceptor distance as well as the detected radical scavenging activity, galangin having more planar stereochemical structure and random B-ring rotation always had higher affinity for caseinate than genistein having location isomerism and twisted stereochemical structure, while the caseinate-galangin complex showed higher radical scavenging activity than the caseinate-genistein complex. It is thus concluded that both chemical and stereochemical structures of polyphenols are crucial to the affinity of polyphenols for protein and antioxidant activities of the protein-polyphenol complexes.

14.
Foods ; 8(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450792

RESUMO

The non-covalent interactions between a commercial whey protein isolate (WPI) and two bioactive polyphenols galangin and genistein were studied at pH 6.8 via the multi-spectroscopic assays and molecular docking. When forming these WPI-polyphenol complexes, whey proteins had changed secondary structures while hydrophobic interaction was the major driving force. Detergent sodium dodecyl sulfate destroyed the hydrophobic interaction and thus decreased apparent binding constants of the WPI-polyphenol interactions. Urea led to hydrogen-bonds breakage and protein unfolding, and therefore increased apparent binding constants. Based on the measured apparent thermodynamic parameters like ΔH, ΔS, ΔG, and donor-acceptor distance, galangin with more planar stereochemical structure and random B-ring rotation showed higher affinity for WPI than genistein with location isomerism and twisted stereochemical structure. The molecular docking results disclosed that ß-lactoglobulin of higher average hydrophobicity had better affinity for the two polyphenols than α-lactalbumin of lower average hydrophobicity while ß-lactoglobulin possessed very similar binding sites to the two polyphenols. It is concluded that polyphenols might have different non-covalent interactions with food proteins, depending on the crucial polyphenol structures and protein hydrophobicity.

15.
Cancer Res ; 79(7): 1383-1397, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683654

RESUMO

The metabolic activity of fumarase (FH) participates in gene transcription linking to tumor cell growth. However, whether this effect is implicated in lung cancer remains unclear. Here, we show TGFß induces p38-mediated FH phosphorylation at Thr 90, which leads to a FH/CSL (also known as RBP-Jκ)/p53 complex formation and FH accumulation at p21 promoter under concomitant activation of Notch signaling; in turn, FH inhibits histone H3 Lys 36 demethylation and thereby promotes p21 transcription and cell growth arrest. In addition, FH is massively phosphorylated at the Ser 46 by PAK4 in non-small cell lung cancer (NSCLC) cells, and PAK4-phosphorylated FH binds to 14-3-3, resulting in cytosolic detention of FH and prohibition of FH/CSL/p53 complex formation. Physiologically, FH Ser 46 phosphorylation promotes tumorigenesis through its suppressive effect on FH Thr 90 phosphorylation-mediated cell growth arrest in NSCLC cells and correlates with poor prognosis in patients with lung cancer. Our findings uncover an uncharacterized mechanism underlying the local effect of FH on TGFß-induced gene transcription, on which the inhibitory effect from PAK4 promotes tumorigenesis in lung cancer. SIGNIFICANCE: Fumarase counteracts CSL via its metabolic activity to facilitate TGFß-induced cell growth arrest, an effect largely blocked by PAK4-mediated phosphorylation of fumarase.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Fumarato Hidratase/metabolismo , Neoplasias Pulmonares/patologia , Linfotoxina-alfa/fisiologia , Quinases Ativadas por p21/metabolismo , Proteínas 14-3-3/metabolismo , Células A549 , Animais , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas F-Box/metabolismo , Xenoenxertos , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/metabolismo , Linfotoxina-alfa/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , Fosforilação , Ligação Proteica
17.
Cell Death Discov ; 4: 44, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30302278

RESUMO

Aberrant activation of signal transducer and activator of transcription 3 (STAT3) plays a critical role in the proliferation and survival of multiple myeloma. And inactivation of STAT3 is considered a promising strategy for the treatment of multiple myeloma. Here we show that the sinomenine derivative YL064 could selectively reduce the cell viability of multiple myeloma cell lines and primary multiple myeloma cells. Moreover, YL064 also induces cell death of myeloma cells in the presence of stromal cells. Western blot analysis showed that YL064 inhibited the constitutive activation and IL-6-induced activation of STAT3, reflected by the decreased phosphorylation of STAT3 on Tyr705. Consistent with this, YL064 inhibited the nuclear translocation of STAT3 and the expression of STAT3 target genes, such as cyclin D1 and Mcl-1. Using biotin- and FITC-labeled YL064, we found that YL064 could pull-down STAT3 from myeloma cells and colocalized with STAT3, suggesting that YL064 directly targets STAT3. Cellular thermal shift assay further demonstrated the engagement of YL064 to STAT3 in cells. Molecular docking studies indicated that YL064 may interact with STAT3 in its SH2 domain, thereby inhibiting the dimerization of STAT3. Finally, YL064 inhibited the growth of human myeloma xenograft in vivo. Taken together, this study demonstrated that YL064 may be a promising candidate compound for the treatment of multiple myeloma by directly targeting STAT3.

18.
PLoS One ; 10(7): e0132337, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26134508

RESUMO

Synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) has been shown as a promising agent against ovarian cancer. However, the underlying mechanism is not well understood. Here, we demonstrate that CDDO-Me directly interacts with Hsp90 in cells by cellular thermal shift assay. CDDO-Me treatment leads to upregulation of Hsp70 and degradation of Hsp90 clients (ErbB2 and Akt), indicating the inhibition of Hsp90 by CDDO-Me in cells. Knockdown of Hsp90 significantly inhibits cell proliferation and enhances the anti-proliferation effect of CDDO-Me in H08910 ovarian cancer cells. Dithiothreitol inhibits the interaction of CDDO-Me with Hsp90 in cells and abrogates CDDO-Me induced upregulation of Hsp70, degradation of Akt and cell proliferation inhibition. This suggests the anti-ovarian cancer effect of CDDO-Me is possibly mediated by the formation of Michael adducts between CDDO-Me and reactive nucleophiles on Hsp90. This study identifies Hsp90 as a novel target protein of CDDO-Me, and provides a novel insight into the mechanism of action of CDDO-Me in ovarian cancer cells.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Ácido Oleanólico/análogos & derivados , Neoplasias Ovarianas/patologia , Antineoplásicos/química , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ditiotreitol/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes erbB-2 , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estrutura Molecular , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Ácido Oleanólico/antagonistas & inibidores , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor ErbB-2/biossíntese , Relação Estrutura-Atividade , Transfecção , Regulação para Cima/efeitos dos fármacos
19.
PLoS One ; 9(8): e104985, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25115845

RESUMO

Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment.


Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Catalase/antagonistas & inibidores , Óxidos/farmacologia , Peroxirredoxinas/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/genética , Apoptose/fisiologia , Trióxido de Arsênio , Catalase/genética , Catalase/metabolismo , Linhagem Celular Tumoral , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
Shanghai Kou Qiang Yi Xue ; 21(4): 470-3, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23135128

RESUMO

PURPOSE: To compare the masticatory efficiency of lingualized occlusal complete denture with that of semi-anatomical occlusal complete denture. METHODS: Sixty cases with flat or depressed residual ridges were selected from 2009 to 2011. After randomly divided into two groups, the patients were treated with lingualized and semi-anatomical occlusal complete dentures, respectively. A comparative study of masticatory efficiency was carried out on patients wearing lingualized occlusal complete dentures with those wearing semi-anatomical occlusal complete dentures in different period (1st, 2nd, 3rd, 6th month) after wearing. SAS6.16 software package was used for data analysis. RESULTS: Once masticatory time or masticatory times were fixed, there was no significant difference between lingualized occlusal dentures and semi-anatomical occlusal complete dentures (P>0.05). CONCLUSION: Lingualized occlusal complete denture can achieve good masticatory efficiency for edentulous patients with flat or depressed residual ridges.


Assuntos
Planejamento de Dentadura , Prótese Total , Mastigação , Humanos , Boca Edêntula
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