• Title/Summary/Keyword: Protein p53

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Inhibitory Effects of Phenolic Alkaloids of Menispermum Dauricum on Gastric Cancer in Vivo

  • Zhang, Hong-Feng;Wu, Di;Du, Jian-Kuo;Zhang, Yan;Su, Yun-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10825-10830
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    • 2015
  • The present study was conducted to investigate effects and mechanisms of action of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo. In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed using fluorescence staining. In vivo, a mice model was constructed to observe tumor growth with different doses. Cell apoptosis was examined using flow cytometry and K-RAS protein expression using Western blotting. The mRNA expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR. PAMD significantly suppressed tumor growth in the xenograft model of gastric cancer in a dose-dependent manner (p<0.01). Functionally, PAMD promoted cell apoptosis of the SGC-7901 cells and significantly increased the rate of cell apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the expression of oncogenic K-RAS both at the mRNA and protein levels. In addition, PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL-2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3.

Tumor necrosis factor-inducible gene 6 interacts with CD44, which is involved in fate-change of hepatic stellate cells

  • Wang, Sihyung;Kim, Jieun;Lee, Chanbin;Jung, Youngmi
    • BMB Reports
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    • v.53 no.8
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    • pp.425-430
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    • 2020
  • Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown. Cluster of differentiation 44 (CD44) is a transmembrane protein that has multiple functions depending on the ligand it is binding, and it is involved in various signaling pathways, including the Wnt/β-catenin pathway. Given that β-catenin influences stemness and acts downstream of CD44, we hypothesized that TSG-6 interacts with the CD44 receptor and stimulates β-catenin to activate YAP-1 during TSG-6-mediated transdifferentiation of HSCs. Immunoprecipitation assays showed the interaction of TSG-6 with CD44, and immunofluorescence staining analyses revealed the colocalization of TSG-6 and CD44 at the plasma membrane of TSG-6-treated pHSCs. In addition, TSG-6 treatment upregulated the inactive form of phosphorylated glycogen synthase kinase (GSK)-3β, which is a negative regulator of β-catenin, and promoted nuclear accumulation of active/nonphosphorylated β-catenin, eventually leading to the activation of YAP-1. However, CD44 suppression in pHSCs following CD44 siRNA treatment blocked the activation of β-catenin and YAP-1, which inhibited the transition of TSG-6-treated HSCs into stem-like cells. Therefore, these findings demonstrate that TSG-6 interacts with CD44 and activates β-catenin and YAP-1 during the conversion of TSG-6-treated pHSCs into stem-like cells, suggesting that this novel pathway is an effective therapeutic target for controlling liver disease.

CoMFA Analysis on Inhibitory Effect of $3{\beta}$-Hydroxy-12-oleanen-28-oic Acid Analogues on PTP-1B Activity and Prediction of Active Compounds ($3{\beta}$-Hydroxy-12-oleanen-28-oic Acid 유도체들의 PTP-1B 저해활성에 대한 CoMFA 분석과 활성 분자들의 예측)

  • Kim, Sang-Jin;Kim, Se-Gon;Sung, Nack-Do
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.34 no.2
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    • pp.109-115
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    • 2008
  • The comparative molecular field analyses(CoMFA) models between the substituents with changing groups($R_1{\sim}R_4$) of $3{\beta}$-hydroxy-12-oleanen-28-oic acid derivatives as substrate molecule and their inhibitory activities($pI_{50}$) against protein tyrosine phosphatase(PTP)-1B were derived and discussed quantitatively. The optimized CoMFA F1 model have best predictability and fitness($r^2_{cv.}=0.654$ and $r^2_{ncv.}=0.995$). The order of contribution ratio (%) with CoMFA fields on the inhibitory activities was a steric field(53.0%), electrostatic field(36.2%) and hydrophobic field(10.8%). From the analytical results of CoMFA contour maps, the inhibitory activities were dependent on the R4 group in substrate molecules. Particularly, the new active compounds(P1 & P2) with the inhibitory activity against melanin synthesis were expected.

A Comparison Study on Functional Properties of Mungbean Protein and Chemically Modified Mungbean Protein (분리 녹두 단백질과 이를 화학적으로 수식화한 단백질간의 식품학적 기능성 비교)

  • Sohn, Kyung-Hee;Min, Sung-Hee;Park, Hyun-Kyung;Park, Jin
    • Korean journal of food and cookery science
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    • v.7 no.3
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    • pp.53-59
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    • 1991
  • This study was carried out in order to investigate the change of protein functionalities such as foaming and emulsifying properties by succinylation of protein isolates. Succinylated and unsuccinylated munghean protein isolates were tested for finding out the effects of pH, heat treatment and sodium chloride concentration on the solubility, emulsion capacity, emulsion stability, foaming capacity, and foam stability. The results are summarized as follows: 1. Succinylation enhanced the solubility of MPI except at pH 4.5. When heated, succinylation greatly increased the solubility of succinylated MPI above $60^{\circ}C$. With the addition of NaCl, succinylation increased the solubility of MPI at acidic condition. 2. Emulsion capacity of succinylated MPI showed the lowest value at pH 7 and higher values at acidic and alkaine condition. when succinylated MPI was heated, emulsion capacity showed the highest at $80^{\circ}C$. With NaCl was added, emulsion capacity of succinylated MPI lincreased at pH 7, 9 or 11 decreased at pH 3 except addition of 1.0M NaCl. 3. Emulsion stability of MPI and succinylated MPI showed the highest at pH 4.5. Succinylation enhanced the emulsion stability of MPI at acidic condition. 4. The foaming capacity of MPI was increased at pH 3, 7 or 9 by succinylation. 5. When heated, foam stability of MPI and succinylated MPI showed the highest at pH 4.5 and at pH 11, respectively. When heated, both proteins showed the highest stability at $100^{\circ}C$.

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Inhibitory Effect of Bojungbangam-tang Kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells (보정방암탕가감방(保正防癌湯加減方)이 cisplatin으로 유도된 인간 근위세뇨관 HK-2세포의 G2/M phase arrest에 미치는 영향)

  • Park, Sung-Cheul;Lee, Su-Kyung;Yeom, Seung-Ryong;Kwon, Young-Dal;Song, Yung-Sun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1555-1563
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    • 2007
  • To idenifty effect of Bojungbangam-tang kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells. Cytotoxicity of cisplatin was detected in HK-2 cells and the value of IC50 is about $25\;{\mu}M$. The treatment of cisplatin to HK-2 showed the G2/M phase cell cycle arrest. The ethanol extract of Bojungbangam-tang kakambang (EBTKB), a new herbal prescription composed of ten crude herbs, inhibited cisplatin-induced G2/M phase arrest in HK-2 cells. EBTKB increased G0/G1 peak in cisplatin-treated HK-2 cells. p53, p21 and p27 expression were increased in cisplatin-treated HK-2 cells. Inhibitory effect of EBTKB on cisplatin-induced G2/M phase arrest was accomplished through inhibition of p53, p21 and p27 expression. Also, reduced CDK2 and cyclin A expression by cisplatin were increased by EBTKB, but cyclin E was not changed. Reduction of ERK activation and increment of p38 activation by cisplatin were increased ERK activation and decreased p38 activation by EBTKB. Cisplatin had no effect on JNK activation, but EBTKB increased JNK activation. These results can suggest that EBTKB inhibits cisplatin-induced G2/M phase arrest in HK-2 cell through reduction of p53-dependent p21 and p27 protein, ERK activation and p38 inactivation.

Studies on Milk Protein of Korean Cattle I. Fractionation of Milk Protein on DEAE-Cellulose (한우유(韓牛乳)의 단백질(蛋白質)에 관(關)한 연구(硏究) 제(第)1보(報) DEAE-Cellulose에 의(依)한 한우유단백질(韓牛乳蛋白質)의 분별(分別))

  • Kim, Y.K.;Chang, J.I.
    • Korean Journal of Food Science and Technology
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    • v.6 no.2
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    • pp.75-78
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    • 1974
  • An experiment has been carried out in order to analyze the main components of Korean Cattles' milk, and fractionate the milk protein by DEAE-cellulose column. The results obtained were summarized as follow. 1) The average values of specific gravity, pH and acidity of Korean Cattles milk which were negative in alcohol test were 1,036, 6.4 and 0.21, respectively. 2) The average values of total solids, solids-not-fat, protein, lactose and ash contents of Korean Cattles milk were 11.61%, 9.53%, 2.08%, 3.99%, 4.76% and 0.86%, respectively. 3) Distribution of casein, whey protein, N.P.N., protein precipitated in 12% TCA, lactoglobulin and lactalbumin contents of the milk were 3.07%, 1.13%, 0.10%, 4.06%, 0.34% and 0.66%, respectively. 4) Acid casein obtained from Korean Cattles milk was fractionated into four fractions on DEAE-cellulose column with 0.005M tris-citrate buffer containing 6M urea, pH 8.6, and the ratio of the fraction I, II, III and IV was 3.24%, 52.67%, 26.22% and 17.87%, respectively. 5) Whey protein obtained from Korean Cattles milk was also fractionated into four fractions on DEAE-cellulose column with 0.04M phosphate buffer, pH 5.8, and the ratio of the fraction I, II, III and IV was 41.74%, 10.17%, 1.50% and 46.59%, respectively.

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High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia

  • Bhatia, Prateek;Masih, Shet;Varma, Neelam;Bansal, Deepak;Trehan, Amita
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6663-6668
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    • 2015
  • Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

Econazole Induces p53-Dependent Apoptosis and Decreases Metastasis Ability in Gastric Cancer Cells

  • Choi, Eun Kyoung;Park, Eun Jung;Phan, Tien Thuy;Kim, Hea Dong;Hoe, Kwang-Lae;Kim, Dong-Uk
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.370-379
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    • 2020
  • Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

Composition of Mineral Contents in Korean Cow무s Milk (우리나라 일부 우유의 무기질 함량 조성에 관한 연구)

  • 이영희;정문호
    • Journal of Environmental Health Sciences
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    • v.30 no.1
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    • pp.29-40
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    • 2004
  • This study was performed to investigate and assess the composition of mineral and macronutrient contents in Korean cow′s milk.48 individual farm raw milk, 10 plant raw milk and 29 market milk were collected from June to August in 2003. The minerals such as calcium(Ca), potassium(K), magnesium(Mg), sodium(Na), zinc(Zn), iron(Fe) and phosphorus(P) were determined by using atomic absorption spectrometer(AAS). The macronutrients such as fat, protein and lactose were tested by using IR spectrometer. The obtained analytical results of minerals(mg/100 g) and rnaetronutrients (%) are as follows:1. In case of raw cow′s milk ; Ca 113.56, K 144.09, Mg 10.86, Na 42.53, Zn 0.42, Fe 0.030, p 113.32, fat 3.85, protein 3.08, lactose 4.80,2. In case of market cow′s milk ; Ca 103.04, K 142.46, Mg 10.27, Na 43.21, Zn 0.40, Fe 0.034. p 97.30, fat 3.78, protein 3.05, lactose 4.70,3. In case of fortified market cow′s milk ; Ca 165.40, K 145.79, Mg 10.57. Na 42.55, Zn 0.57, Fe 0.414, p 94.68, fat 3.74, protein 3.08, lactose 4.68,4. In case of processed market cow′s milk ; Ca 134.72, K 142.74, Mg 10.33, Na 45.07, Zn 0.50, Fe 0.650, p 92.48, fat 3.72, protein 3.07, lactose 4.74. According to the group of market milk(milk, fortified market row′s milk, processed market cow′s milk), the mean concentration of Ca and Fe were significantly higher in fortified and processed milk than milk(p<0.05). There were no significant differences in macronutrient(fat, protein, lactose) and mineral contents between pasteurized milk and UHT(ultra high temperature) treated milk($\alpha$=0.05). The labeled "Nutritional Facts" of market milk were satisfied with "Labeling Standards for Livestock Products of Korea". The measured mean concentrations of Ca, Fe, Zn were generally higher than lower limit of labeled value(above 80% of labeled value). The mean concentration of sodium was lower than upper limit of labeled value(below 120% of labeled value).

Blood amino acids profile responding to heat stress in dairy cows

  • Guo, Jiang;Gao, Shengtao;Quan, Suyu;Zhang, Yangdong;Bu, Dengpan;Wang, Jiaqi
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.1
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    • pp.47-53
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    • 2018
  • Objective: The objective of this experiment was to investigate the effects of heat stress on milk protein and blood amino acid profile in dairy cows. Methods: Twelve dairy cows with the similar parity, days in milk and milk yield were randomly divided into two groups with six cows raised in summer and others in autumn, respectively. Constant managerial conditions and diets were maintained during the experiment. Measurements and samples for heat stress and no heat stress were obtained according to the physical alterations of the temperature-humidity index. Results: Results showed that heat stress significantly reduced the milk protein content (p<0.05). Heat stress tended to decrease milk yield (p = 0.09). Furthermore, heat stress decreased dry matter intake, the concentration of blood glucose and insulin, and glutathione peroxidase activity, while increased levels of non-esterified fatty acid and malondialdehyde (p<0.05). Additionally, the concentrations of blood Thr involved in immune response were increased under heat stress (p<0.05). The concentration of blood Ala, Glu, Asp, and Gly, associated with gluconeogenesis, were also increased under heat stress (p<0.05). However, the concentration of blood Lys that promotes milk protein synthesis was decreased under heat stress (p<0.05). Conclusion: In conclusion, this study revealed that more amino acids were required for maintenance but not for milk protein synthesis under heat stress, and the decreased availability of amino acids for milk protein synthesis may be attributed to competition of immune response and gluconeogenesis.