• Journal of Veterinary Science
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• 제22권5호
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• pp.61.1-61.13
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• 2021

Background: Hepatocellular carcinoma is the most common primary hepatic malignancy in humans and dogs. Several differentially expressed molecules have been studied and reported in human hepatocellular carcinoma and non-neoplastic liver lesions. However, studies on the features of canine hepatocellular carcinoma are limited, especially related to the differential characteristics of neoplastic and non-neoplastic lesions. Objectives: The study's objective was 1) to examine and evaluate the expression of arginase-1, P-glycoprotein, and cytokeratin 19 in canine liver tissues and 2) to investigate the differential features of hepatocellular carcinomas, liver tissue with non-neoplastic lesions, and paracancerous liver tissues in dogs. Methods: The expression levels of three markers underwent immunohistochemical analysis in 40 non-neoplastic liver tissues, 32 hepatocellular carcinoma tissues, and 11 paracancerous liver tissues. Scoring of each marker was performed semi-quantitatively. Results: Arginase-1 and P-glycoprotein were significantly downregulated in hepatocellular carcinoma, compared with hepatic tissues with non-neoplastic diseases (p < 0.001). Expression levels of arginase-1 and P-glycoprotein were also significantly lower in hepatocellular carcinoma than in paracancerous liver tissues (arginase-1, p = 0.0195; P-glycoprotein, p = 0.047). Few cytokeratin 19-positive hepatocytes were detected and only in one hepatocellular carcinoma and one cirrhotic liver sample. Conclusions: The results of this study suggest that downregulation of arginase-1 and P-glycoprotein is a feature of canine hepatocellular carcinoma; thus, those markers are potential candidates for use in differentiating hepatocellular carcinomas from non-neoplastic liver lesions in dogs.

• 한국환경과학회지
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• 제28권2호
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• pp.249-257
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• 2019

Ulmus davidiana Nakai (UDN) has been traditionally used as a herbal medicine to treat inflammatory diseases in Korea. In the present study, we investigated the anti-ecotoxic potential of a 116 kDa glycoprotein isolated from UDN (UDN glycoprotein) in human intestinal epithelial INT-407 cells. We demonstrated that UDN glycoprotein ($20{\mu}g/mL$) could inhibit the production of lactate dehydrogenase (LDH) induced by toluene, an ecotoxic substance. Additionally, we found that the toluene-induced intestinal cytotoxicity was mediated by the phosphorylation of p38 Mitogen-Activated Protein Kinase (MAPK) via the production of intracellular Reactive Oxygen Species (ROS). The UDN glycoprotein significantly decreased the levels of ROS production and p38 MAPK activation in toluene-stimulated INT-407 cells. Moreover, the UDN glycoprotein inhibits the phosphorylation of nuclear factor-kappa B ($NF-{\kappa}B$), which is responsible for the production of LDH, in toluene-stimulated INT-407 cells. Collectively, our data indicate that UDN glycoprotein is a natural antioxidant and a modulator of ecotoxicity signaling pathways in human intestinal epithelial cells.

• Journal of the Korean Wood Science and Technology
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• 제32권5호
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• pp.51-58
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• 2004

본 연구에서는 능이가 포함하고 있는 각종 생리활성 성분올 분석하고, 열수추출-에틸알코올 침전에 의하여 분리한 glycoprotein 의 특성을 구명코자 하였다. 능이(Sarcodon aspratus)의 무기성분 및 아미노산의 조성을 분석하였는 바, 능이는 Ca, Mg, Zn, Mn, Fe, Cu 및 Ph를 함유하였으며, 특히 Ca 및 Na 성분이 많이 함유되어 있었다. 유리 및 총 아미노산을 분석한 결과, 14종의 유리아미노산이 검출되었고. glutamic acid, alanine, arginine 등이 많았다. 총아미노산은 15종이었으며, glutamic acid가 가장 많았고, aspartic acid, serine, threonine 등이 그 다음이었다. 열수-95% 에틸알코올 추출에 의하여 70.6%의 당과 3.32%의 glycoprotein을 얻었으며, 에틸알코올의 농도에 따라 당의 함량이 상이한 glycoprotein을 얻을 수 있었는데, 에틸알코올의 농도가 30~70%로 낮은 경우, 당함량이 92% 이상으로 매우 높았다. 조 glycoprotein (GP). 분자량 30만 이상의 분획(P), P분획 가운데 DEAE-Sephadex에 흡착되지 않는 분획(P-1), P-1을 다시 Sepharose 2B로 젤여과하여 얻은 부분(P-2), DEAE-Sephadex에 흡착되는 부분 (P-3) 등으로 분획한 결과, 정제과정에서 total sugar의 함량은 점차 증가하였으며, 단백질의 함량은 점차 감소되는 것으로 나타났다. 단당류의 조성을 분석한 결과, GP 빛 P-3 에서 glucose, galactose, mannose, fucose 등 4종의 당이 검출 되었으며, GP에는 glucose 가 거의 대부분을 이루고 있었고, glutamic acid, serine, alanine, glycine 등이 고농도로 함유되어 있었다. P-3에는 mannose 및 aspartic acid, glutamic acid, glycine 등의 아미노산이 함유되어 있었다. P-2에서는 glucose가 많았고, 다른 fraction에는 없었던 fucose의 함량이 높았으며 mannose는 검출되지 않았다. 한편 아미노산조성은 조 glycoprotein (GP)에는 glutamic acid, serine, alanine, glycine 등이 고농도로 함유되었으며, P-3분획에서는 aspartic acid, glutamic acid, glycine 등이 함유되어 있었다. 한편 P-2 fraction의 경우는 단백질함량이 1.1%로서 매우 낮았으며, 분자량은 700,000 이상이었다. aspartic acid, glutamic acid, alanine이 비교적 다량 함유되었으며, mannose 및 cysteine은 거의 확인되지 않았다.

• Natural Product Sciences
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• 제20권1호
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1639-1642
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• 2014

The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 ${\mu}M$) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 ${\mu}M$) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.

• 통합자연과학논문집
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• 제4권1호
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6831-6839
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• 2015

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

• Journal of Microbiology
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• 제34권1호
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• pp.7-14
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• 1996

Teh baculovirus gp64 glycoprotein is a major component of the envelope of budded virus (BV) and has been shown that it plays an essential role in the infection process, especially virus-cell membrane fusion. We have cloned Autographa californica Nuclear Polyhedrosis Virus (AcNPV) gp64 protein were examined for membrane fusion activity by using a synchtium formation assay under various conditions. The optimal conditions required for inducing membrane fusion are 1) form pH 4.0 to 4.8 2) 15 min exposure of cells to acidic pH 3) at least 1 .mu.g of gp64 cloned plasmid DNA per 3 * 10$^{6}$ cells 4) and an exposure of cells to acidic pH at 72 h post-transfection. In order to investigate the role of hydrophobicity of the gp64 glycoprotein for the membrane fusion, the two leucine residues (amino acid position at 229 and 230) within hydrophobic region I were substituted to alanine by PCR-derived site-directed mutagenisis and the membrane fusion activity of the mutant was anlaysed. The gp64 glycoprotein carrying double alamine substitution mutation showed no significant difference in fusion activity. This result suggested that minor changes in hydrophobicity at the amino acid position 229 and 230 does not affect the acid-induced membrane fusion activity of the gp64 glycoprotein.

• Advances in Traditional Medicine
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• 제8권3호
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• pp.207-214
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• 2008

In recent years, the combined use of Herbal medicines and Western drugs has been increasing. Though certain problems may occur when both types of medicines are taken together, they havenot been adequately analyzed. It was reported that anticoagulation was enhanced in addition tobleeding when patients took long-term warfarin therapy in combination with Salvia miltiorrhiza(danshen), and laxative herbs accelerate intestinal transit and interfere with the absorption. Herbal constituents, curcumin, ginsenosides, piperine, catechins and silymarin were found to beinhibitors of P-glycoprotein. St John's wort induces the intestinal expression of P-glycoprotein. Anthraquinone, quercetin and coumarins were found to be a potent inhibitor of P-450. Glycyrrhizin or liquorice extracts, Garlic and St John's wort are a potent inducer of CYP3A4. This review provides a critical overview of interactions between herbal medicines and other drugs. Hence, it is necessary to study the pharmacodynamic and pharmacokinetic interactions of many herbal medicines between western drugs.

• 한국식품과학회지
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• 제37권4호
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• pp.624-630
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• 2005

본 연구는 천연물에서의 생리활성물질 동정의 일환으로 Ficus Carica Linnoeus(FCL)로부터 60kDa의 FCL glycoprotein(무화과 당단백질)을 추출한 후, 무화과 당단백질의 첨가에 따른 과산화 지질 라디칼 억제능력 및 생질의 혈장 콜레스테롤 수준과 간 해독효소활성의 개선효과를 평가하였다. In vitro에서 리놀렌산 자동산화반응에 기초한 과산화 지질 라디칼 억제능력을 실험한 결과, 무화과 당단백질을 섭취시킨 농도가 증가함에 따라 과산화 지질 라디칼 억제율은 증가하였다. 한편, 생쥐에게 14일 동안 무화과 당단백질을 50 및 100mg/kg 농도로 섭취시킨 그룹과 무화과 당단백질을 섭취시킨 후 Triton WR-1339를 투여한 생쥐 그룹에서 혈액 및 간조직을 채취하여 혈장 콜레스테롤의 수준변화 및 해독효소의 활성을 측정한 결과, 100mg/kg 농도로 무화과 단백질을 섭취시킨 그룹에서 TC와 LDL-콜레스테롤의 수준은 유의적 감소효과가 나타났다(p<0.05). 또한 Triton WR-1339에 의해 고지혈증이 유발된 생쥐그룹에서도 TC와 LDL-콜레스테롤 수준이 유의적 억제능력을 보였는데, 특히 100mg/kg 농도에서 그 개선 효과는 더욱 분명하였다(p<0.01). 간의 해독효소 중 항산화 기능을 하는 SOD, CAT 그리고 GPx의 활성은 모두 증가되었는데, 특히 GPx는 100mg/kg의 농도에서 유의성을 보이며 증가하였다(p<0.01). 따라서 이러한 결과를 종합하면, 무화과 당단백질이 해득효소의 활성을 증가시킴으로써 체내의 ROS의 수준을 감소시키고, 이러한 항산화 효과가 혈중 콜레스테롤의 수준을 감소시키는데 영향을 미친 것으로 사료된다.