• 제목/요약/키워드: P-Glycoprotein

검색결과 335건 처리시간 0.023초

The inhibitory mechanism of crude saponin fraction from Korean Red Ginseng in collagen-induced platelet aggregation

  • Jeon, Bo Ra;Kim, Su Jung;Hong, Seung Bok;Park, Hwa-Jin;Cho, Jae Youl;Rhee, Man Hee
    • Journal of Ginseng Research
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    • 제39권3호
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    • pp.279-285
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    • 2015
  • Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

Correlation of Inhibin and Several Antioxidants in Children with Acute Lymphoblastic Leukemia

  • Mehde, Atheer Awad;Mehdi, Wesen Adel;Zainulabdeen, Jwan Abdulmohsin;Abdulbari, Alaa Shawqi
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.4843-4846
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    • 2014
  • Background: Acute lymphoblastic leukemia (ALL) is most common in childhood. Inhibin (a non-steroidal glycoprotein hormone of gonadal origin) can be used as marker of fertility. The current study was conducted to evaluate inhibin levels in ALL patients and to estimate its correlation with some antioxidants in these in comparison with control subjects. Materials and Methods: This study was conducted on sixty patients with ALL and thirty children as controls. Fasting blood samples were taken from each subject and analyzed for haemoglobin, serum protein, vitamin E and C, in addition to glutathione and inhibin. Results: The results of the study showed highly significant decreases (p<0.001) in haemoglobin, glutathione and inhibin levels with significant decreases (p<0.05) in serum protein and vitamin E levels for patients group in comparison with controls while there was no significant differences in vitamin C. Moreover, there were significant correlations between inhibin levels and serum protein, glutathione and both vitamins (E and C) in the ALL patient group (r= 0.81, 0.80, 0.77 and 0.69, respectively). Conclusions: The present results indicated infertility in patients with ALL demonstrated by low inhibin level as a consequence of abnormality in anti-oxidative metabolism due to the cancer process. So, it can be suggested the need for routine measurement of inhibin for leukemic patients to estimate the action of hormones of gonadal origin.

Comparative Study of Gene Expression Profiles in Posterior Silk Glands of the Silkworm, Bombyx mori L.

  • Choi, Kwang-Ho;Goo, Tae-Won;Kang, Seok-Woo;Kang, Min-Uk;Yun, Eun-Young;Hwang, Jae-Sam
    • International Journal of Industrial Entomology and Biomaterials
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    • 제17권2호
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    • pp.229-234
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    • 2008
  • We used serial analysis of gene expression (SAGE) approach to derive a profile of expressed genes of the posterior silk glands (PSG) and to create a reference for understanding gene cluster related to the mechanism of silk protein synthesis in the silkworm, Bombyx mori. We constructed a 3' SAGE library from the PSG of the fifth instar larvae of the silkworm. In total we obtained 2,406 SAGE tags, of which 682 were unique tags. Sorted by tag count number, 27 (4%) unique tags were significantly more abundant genes (ten or more times), whereas 445 (65%) unique tags were detected as single copies. The annotation of 682 unique SAGE tags revealed that 462 (68%) of the SAGE tag sequences represented known genes, whereas 220 (32%) of the tag sequences had no matches in SAGE map and silkworm EST databases. Of the 682 SAGE tags, the most abundant tag sequences were that of the fibroin light chain gene and the silk protein P25. In addition, we compared two relative abundance results of the SAGE and the EST approaches to verify whether their transcript quantitative aspects are significant or not. The comparative results of relative abundances of the fibroin H-, L- chain and P25 glycoprotein genes indicated that the quantitative approach based on SAGE tags is effective for quantitative cataloging and comparison of expressed genes in same organs. The SAGE tag information reported in this study would be useful for researchers in the field to analyze genes associated with silk processing mechanisms of insects.

Parasitism of the protozoan Perkinsus atlanticus in Manila clams, Ruditapes philippinarum, in Gomso Bay (Korea) and Ariake Bay (Japan)

  • Park, Kyung-Il;Choi, Kwang-Sik;Ngo, Thao T.T.;Tsutsumi, Hiro;Hong, Jae-Sang
    • 한국양식학회:학술대회논문집
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    • 한국양식학회 2004년도 수산관련학회 공동학술대회 발표요지집
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    • pp.513-513
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    • 2004
  • Manila clam, Ruditapes philippinarum, is commercially and ecologically important marine bivalve in Korea and japan. However, clam landings in the two countries have dramatically declined since the 1980-1990's. In the present study, the protozoan parasite, Perkinsus sp., lectin (host's defense-related glycoprotein) and histopathological features were investigated in Manila clams collected from Gomso Bay in Korea and Ariake Bay in japan (one of the largest clam beds in each country) during summer and fall, 2002-2003. DNA sequences of non-transcribe spacer (NTS), internal transcribed space. (ITS) and 5.85 rRNA of Perkinsus sp. were identical to those of P. atlanticus that was reported in Europe and Korea. For diagnosis of Perkinsus, the fluid thioglycollate medium (FTM) and the 2 M NaOH lysis methods were used. Prevalence of the parasite varied from 92.5-98.7% in Gomso Bay and 35.5-37.9% in Ariake Bay. Infection intensity, in terms of the number of Perkinsuscells per gram tissue wet weight, in the clams of Gomso Bay in fall 2002 averaged 1,010,077-470,937 recording approximately100 times higher than that of Ariake Bay, and these were twice higher than those of summer samples in each location. Mean hemagglutination titer of the clams from Gomso Bay was approximately 60-folds higher than that of clams from Ariake Bay in 2002. In histological preparation of the clams from Gomso Bay in 2002, trophozoites of P. atlanticus were in groups and resulted in severe inflammatory response of host clam. Prevalence of the trematod, Cercaria tapes-like in the clams of Gomso Bay and Ariake Bay were 8.8 % and 10.5% respectively. In conclusion, the clams from Gomso Bay showed more severe pathologic symptoms and higher immune response than those of the clams from Ariake Bay.

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Lack of Association of the MDR1 C3435T Polymorphism with Susceptibility to Gastric Cancer and Peptic Ulcer: a Systemic Review and Meta-analysis

  • Wu, Dan-Dan;Zhang, Ji-Xiang;Li, Jiao;Dong, Wei-Guo
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3021-3027
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    • 2014
  • Background: The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). Materials and Methods: A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. Results: Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. Conclusions: This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.

바지락(Tapes japonica)으로부터 분리정제된 새로운 렉틴의 생물물리학적 특성 (Purification and Biophysical Characterization of New Lectin from Baby Clam, Tapes japonica)

  • 김희숙
    • 한국식품과학회지
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    • 제21권5호
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    • pp.606-612
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    • 1989
  • 한국산 바지락으로부터 새로운 렉틴을 아세톤파우더, 황산암모늄 침전, 친화력 크로마토그라피 및 FPLC의 이온교환 크로마토그라피법으로 분리 정제하였다. 이 렉틴은 사람의 적혈구를 비특이적으로 응집시켰으며, 생쥐와 토끼의 적혈구 및 생쥐의 복수 Sarcoma 180 세포를 응집시키지 않았고 사람의 말초혈관 임파구도 분열 촉진시키지 못하였다. 전기영동상에서 하나의 주된 띠로 나타났으며 분자량은 Biogel P-300겔 여과에서 131,000, SDS 전기영동상에서는 125,000으로 나타났다. Subunit는 33,000과 30,000의 다른 폴리펩타이드로 tetramer로 추정된다. EDTA에 의해서 활성이 저해된 바지락 렉틴은 $Ca^{++}$$Mn^{++}$에 의하여 적혈구 응집력이 회복되었다. 또한 이 렉틴은 약 4.2% 중성당을 함유한 당단백질임이 확인되었다.

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Pleurotus ostreatus에서 분비되는 Peroxidase의 특성 (Characterization of Extracellular Peroxidase from Pleurotus ostreatus)

  • 배성호;신광수;강사욱;하영칠;최선진;김규중;최형태
    • 미생물학회지
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    • 제27권4호
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    • pp.348-356
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    • 1989
  • PIeurotus ostrealus의 배양액에서 syringic acid에 의해 유도되는 peroxidase의 활성이 추정되었다. 본 효소는 DEAE Sephadex A-50 이온교환크로마토그래피와 Sephadex G-150 첼 여과크로마토 그래피를 통하여 순수분리 되었다. 순수분리된 효소는 당함량이 35.7%인 당단백젤이었으며. SDS-linear polyacrylamide gradient gel 전기영동과 젤여과크로마토그래피에 의해 분자량(Mr) 72.400인 2개의 동일한 소단위체로 이루어진 이합체로 판명되었다. 본 효소는 흡광 스펙프럼의 분석결과, iron protoporphyrin IX의 구조를 갖는 2개의 heme을 조효소로 가지고 였는 것으로 추정되였다. 본 효소의 등전점은 4.26 이었고 $H_2O_2$에 대한 $K_m$값은 $7.2{\mu}M$이었다. 본 효소의 반응 최적온도는 $40^{\circ}C$, 최적 pH는 3.5에서 4.0 사이였다. Ferulic acid와 sinapic acid에 대한 본 효소의 친화도(Km)는 horseradish peroxidase에 비해 각각 2.4. 12.3배 더 높은 것으호 계산되었다.

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Chemosensitizing effect and mechanism of imperatorin on the anti-tumor activity of doxorubicin in tumor cells and transplantation tumor model

  • Liang, Xin-li;Ji, Miao-miao;Liao, Zheng-gen;Zhao, Guo-wei;Tang, Xi-lan;Dong, Wei
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권3호
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    • pp.145-155
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    • 2022
  • Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

형질전환 담배 식물체에서 재조합 erythropoietin 유전자의 발현 (Expression of Recombinant Erythropoietin Gene in Transgenic Tobacco Plant)

  • CHOI, Jang Won;PARK, Hee Sung
    • 식물조직배양학회지
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    • 제24권1호
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    • pp.63-69
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    • 1997
  • Erythropoietin(EPO)은 적혈구 모세포의 분화와 성장을 중재하는 당단백질이며 담배 식물체에서 재조합 사람 EPO를 생산하기 위해 CaMV 35S promoter를 갖는 발현 vector인 pBI$\Delta$GUS121, pBD$\Delta$ GUS121, pPEV-1을 이용하여 5.4kb의 EPO genomic DNA를 cloning 하였고 Agrobacterium tumefaciens에 의한 형질전환에 의해 Nicotiana tabacum (var. Xanthi)으로 도입되었다. Kanamycin을 포함하는 MS 배지에서 각각의 construct에 대하여 10 km 저항성 식물체들이 얻어졌다. 형질전환된 식물체의 게놈에 EPO genomic DNA의 정확한 결합은 polymerase chain reaction에 의해 332bP의 DNA 조각에 의해 확인되었으며 Northern blot 결과 1.8 kb의 전사체들이 식물체 잎에서 발현 축적되는 것이 확인되었다. Promoter의 수나 5'-UTS 서열에 의한 mRNA 양에는 변화가 없었지만 식물체 게놈에 결합된 위치 및 copy number에 의해 mRNA 수준에 영향을 주는 것으로 밝혀졌다. EPO 항체를 이용한 Western blot 결과 식물체에서 발현된 EPO 단백질의 크기는 동물세포에서 발현된 37kDa 보다 작은 30 kDa 이었다. 이는 식물체에서 modification(glycosylation) system은 동물세포에서와는 다르다는 것을 보여준다.

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Synthetic Prion Peptide 106-126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells

  • Song, Kib-Beum;Na, Ji-Young;Oh, Myung-Hoon;Kim, Sok-Ho;Kim, Young-Ha;Park, Byung-Yong;Shin, Gi-Wook;Kim, Bum-Seok;You, Myung-Jo;Kwon, Jung-Kee
    • Toxicological Research
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    • 제28권1호
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    • pp.5-9
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    • 2012
  • It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-$1{\beta}$) and tumor necrosis factor alpha (TNF-${\alpha}$) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.