• Title/Summary/Keyword: 대사 억제제

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Effects of dopamine on angiotensin II-induced stimulation of Na+ uptake in primary cultured rabbit renal proximal tubule cells (초대배양한 신장 근위세뇨관세포에서 ANG II의 Na+ uptake 촉진효과에 대한 dopamine의 효과)

  • Koh, Hyun-ju;Park, Soo-hyun;Han, Ho-jae
    • Korean Journal of Veterinary Research
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    • v.38 no.3
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    • pp.518-524
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    • 1998
  • 신장 근위세뇨관세포들은 사구체에서 여과된 물질의 재흡수, 분비 및 대사에 관여하는 여러 호르몬들의 수용체들을 가지고 있다. 이들중에서 dopamine(DA)과 angiotensin II(ANG II)가 $Na^{+}/H^{+}$ 상호운반계 조절에 중요한 역할을 하고 있다. 본 연구는 초대배양한 토끼 신장 근위세뇨관세포의 $Na^+$ uptake에 있어서 DA과 ANG II의 상호관계를 알아보고자 실시하였다. DA은 농도의존적으로 $Na^+$ uptake를 유의성 있게 억제하였다($10^{-6}M$ ; $83.2{\pm}7.2%$, $10^{-3}M$ ; $67.2{\pm}3.8%$ vs. control)(p<0.05). $DA_1$ 작동제(SKF 38393, $10^{-6}M$)는 대조군의 $81.4{\pm}6.7%$ 까지 $Na^+$ uptake를 유의성 있게 억제하였으나(p < 0.05) $DA_2$ 작동제는 영향을 미치지 않았다. $DA_1$ 길항제(SCH 23390, $10^{-6}M$)에 의해 DA의 $Na^+$ uptake 억제효과는 차단되었으나 $DA_2$ 길항제(spiperone, $10^{-6}M$)에 의해서는 영향을 받지 않았다. DA과 대조적으로 $10^{-11}M$ ANG II는 $AT_1$ 수용체를 통하여 대조군의 $120.7{\pm}4.9%$까지 $Na^+$ uptake를 유의성 있게 촉진하였다. (p < 0.05). DA 및 $10^{-11}M$ ANG II를 병합처리하였을 때 DA은 농도의존적으로 ANG II에 유도된 $Na^+$ uptake 촉진효과를 유의성 있게 차단하였다(p<0.05). 한편 ANG II에 의해 유도된 $Na^+$ uptake촉진작용은 $DA_1$ 또는 $DA_2$ 작동제에 의해 차단되었으나 DA에 의한 차단 효과는 $DA_1$$DA_2$ 길항제를 병합처리하였을 때만 반전되었다. 결론적으로 DA은 $DA_1$ 수용체를 통하여 $Na^+$ uptake를 억제하였으나 ANG II에 의한 $Na^+$ uptake 촉진작용의 억제에는 $DA_1$$DA_2$ 수용체 모두가 관여하였다.

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The Distribution of $^{14}C-chitosan$ by Different Molecular Weight in Mice (마우스에서 $^{14}C-chitosan$ 분자량별 체내 분포에 관한 연구)

  • Kim, Kwang-Yoon;Kim, Young-Ho;Kim, Hee-Kyung;Bom, Hee-Seung;Kim, Ji-Yeul;Roh, Young-Bok;Nishimura, Yoshikazu
    • Journal of Radiation Protection and Research
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    • v.23 no.2
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    • pp.83-88
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    • 1998
  • Chitosan is a nontoxic natural chealtor which was made by chitin, and reduced a contamination of radiostrontium in animals. In this experiment, A different molecular weight of C-14 chitosan was intravenously administered to mice, and then the distribution of C-14 chitosan in the body was observed. Male mice (8 to 10 weeks, body weight of 30 to 35g) of ICR strain were used. C-14 chitosan was diluted with saline and then given intravenously in mice. After the administration of C-14 chitosan, mice was sacrificed at the 6th hour, 1st, 3rd, 5th, and 7th day. Beta radioactivities in the blood, liver, kidney, liver, muscle, testis, and urine was measured using a liquid scintillation analyzer. Most of the C-14 chitosan was excreted through urine within 6 hours. Biodistribution of C-14 chitosan was similar despite the difference of moleclar weight. Higher distributions of radioactivities were found in the liver, kidney, spleen. The relative concentration in tissue increased for the 6 hours and then decreased. In conclusion, most of C-14 chitosan was excreted through urine despite the difference of molecular weight. and, low molecular weight of C-14 chitosan showed higher distribution than high molecular weight of C-14 chitosan in tissues.

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Development of "Bt-Plus" Biopesticide Using Entomopathogenic Bacterial (Xenorhabdus nematophila, Photorhabdus temperata ssp. temperata) Metabolites (곤충병원세균(Xenorhabdus nematophila, Photorhabdus temperata ssp. temperata)의 대사물질을 이용한 "비티플러스" 생물농약 개발)

  • Seo, Sam-Yeol;Kim, Yong-Gyun
    • Korean journal of applied entomology
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    • v.50 no.3
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    • pp.171-178
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    • 2011
  • Bacillus thuringiensis (Bt) is a bacterial biopesticide against insect pests, mainly lepidopterans. Spodoptera exigua and Plutella xylostella exhibit significant decreases in Bt susceptibility in late larval instars. To enhance Bt pathogenicity, we used a mixture treatment of Bt and other bacterial metabolites which possessed significant immunosuppressive activities. Mixtures of Bt with culture broths of Xenorhabdus nematophila (Xn) or Photorhabdus temperata ssp. temperata (Ptt) significantly enhanced the Bt pathogenicity against late larval instars. Different ratios of Bt to bacterial culture broth had significant pathogenicities against last instar P. xylostella and S. exigua. Five compounds identified from the bacterial culture broth also enhanced Bt pathogenicity. After determining the optimal ratios, the mixture was applied to cabbage infested by late instar P. xylostella or S. exigua in greenhouse conditions. A mixture of Bt and Xn culture broth killed 100% of both insect pests when it was sprayed twice, while Bt alone killed less than 80% or 60% of P. xylostella and S. exigua, respectively. Other Bt mixtures, including Ptt culture broth or bacterial metabolites, also significantly increased pathogenicity in the semi-field assays. These results demonstrated that the Bt mixtures collectively names "Bt-Plus" can be developed into potent biopesticides to increase the efficacy of Bt.

Preparation and Characterization of Liposome for Iron-Fortified Food Additive (철분 강화 식품첨가제용 리포좀의 제조 및 특성)

  • 이종우;전수진
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.5
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    • pp.864-868
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    • 2004
  • Iron is an essential ingredient for all metabolism in a living body However, because of the very low content of the iron in foods, many researches have been performed about iron-fortified food additives. We developed an iron-fortified food additive using the liposome that contain ferrous sulfate and hemin. For preventing the autoxidation of the ferrous sulfate, ascorbic acid was applied. Also, to prevent the oxidation of the liposome induced by the added ferrous sulfate and/or hemin, $\alpha$ -tocopherol was additionally applied. Though the effect of the added aqueous ascorbic acid did not show the antioxidative activity on the liposome containing ferrous sulfate and/or hemin, the added $\alpha$ -tocopherol in the phospholipid bilayer could retard the oxidation of the liposome. These results support that the liposome containing ferrous sulfate, hemin and ascorbic acid with the incorporated $\alpha$ -tocopherol could be applied in the food industry as an iron-fortified additive.

Natural Quercetin Derivatives: Structures and Biological Activities Based on Enzyme Inhibition (천연물질 퀘르세틴 유도체의 다양한 구조 및 효소 저해 활성)

  • Na Rae Kang;Yun Gon Son;Jeong Yoon Kim
    • Journal of Life Science
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    • v.34 no.9
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    • pp.656-665
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    • 2024
  • Enzymes, as proteins that regulate various metabolic processes within the human body, play a crucial role in maintaining health. However, the overexpression of certain enzymes can disrupt metabolic balance, leading to various diseases. Enzyme inhibitors are vital in treating these diseases or conditions by inhibiting the action of these enzymes, making them indispensable in the development of effective therapies for a wide array of diseases. Quercetin, a natural product derived from plants, is a type of flavonoid that belongs to the polyphenol family. Quercetin, a natural flavonoid from the polyphenol family, has emerged as a potent enzyme inhibitor. This low-molecular-weight secondary metabolite is known for its inhibitory effects on enzymes such as α-glucosidase, acetylcholinesterase, bacterial neuraminidase, and xanthine oxidase due to its structural advantages. Quercetin is isolated from biomaterials and can be classified into glycosylated, methoxylated, and alkylated derivatives based on its structural variations. These natural quercetin derivatives possess unique substituents that enable specific binding patterns with catalytic residues in enzyme active sites. Therefore, quercetin derivatives can be expected to have better enzyme inhibitory activity than basic quercetin. Due to their specificity and enhanced activity, quercetin and its derivatives hold promise as candidates for developing potent enzyme inhibitors to treat diseases resulting from enzyme imbalances.

Degradations of human immunoglobulins and hemoglobin by a 60 kDa cysteine proteinase of Trichomonas vaginalis (질편모충의 60 kDa 시스테인 단백분해효소의 인체 면역글로불린 및 헤모글로빈 분해능)

  • Duk-Young MIN;Keun-Hee Hyun;Jae-Sook Ryu;Myoung-Hee AHN;Myung-Hwan CHO
    • Parasites, Hosts and Diseases
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    • v.36 no.4
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    • pp.261-268
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    • 1998
  • The present study was undertaken to investigate the role of cysteine proteinase of Trichomonas vaginalis in escaping from host defense mechanism. A cysteine proteinase of T. vaginalis was purified by affinity chromatography and gel filtration. Optimum pH for the purified proteinase activity was 6.0. The proteinase was inhibited by cysteine and serine proteinase inhibitors such as E-64, NEM, IAA, leupeptin. TPCK and TLCK, and also by $Hg^{2+}$, but not affected by serine-, metallo-, and aspartic proteinase inhibitors such as PMSF, EDTA and pepstatin A. However, it was activated by the cysteine proteinase activator, DTT. The molecular weight of a purified proteinase was 62 kDa on gel filtration and 60 kDa on SDS-PAGE. Interestingly, the purified proteinase was able to degrade serum IgA, secretory IgA, and serum IgG in time- and dose-dependent manners. In addition, the enzyme also degraded hemoglobin in a dose-dependent manner. These results suggest that the acidic cysteine proteinase of T. vaginalis may play a dual role for parasite survival in conferring escape from host humoral defense by degradation of immunoglobulins, and in supplying nutrients to parasites by degradation of hemoglobin.

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A New Treatment Option for Gaucher Disease Type 1: Substrate Reduction Therapy (제1형 고셔병 환자의 새로운 치료로서의 기질 감소 치료)

  • Sohn, Young Bae
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.3
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    • pp.117-122
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    • 2016
  • 제1형 고셔병(Gaucher disease type 1)은 리소좀 효소인 산성 ${\beta}$-글루코시다아제(acid ${\beta}-glucosidase$)의 결핍으로 인한 리소솜 축적 질환이다. 효소 활성도가 감소되어 기질이 축적되어, 간비종대, 빈혈, 혈소판감소증 및 골질환을 포함한 전신 증상이 발생한다. 재조합 효소 단백을 정맥 주입하는 효소 대체요법(Enzyme replacement therapy)는 지난 20년 넘게 고셔병의 표준 치료법이었다. 그러나 성공적인 효소 대체요법에도 불구하고, 심각한 폐증상과 골격 증상 등 고셔병 치료에 여전히 해결되지 않는 문제들이 남아 있다. 기질 감소 치료(Substrate reduction therapy)는 기질의 생합성을 억제하여 축적을 감소시킨다. 최근 새로운 경구용 기질감소 치료제인 엘리글루스타트(eliglustat)가 적합한 CYP2D6 대사 표현형을 가진 고셔병 성인 환자를 위한 1차 치료제로 미국과 유럽에서 승인되었다. 엘리글루스타트가 아직 한국에서는 쓰이지 않고 있지만, 본 종설에서는 문헌 검토를 통해 고셔병의 새로운 치료로서의 효소 대체요법을 소개하고자 한다. 아직 확고한 결론을 도출하기에는 연구 결과가 제한적이기는 하지만, 현재까지의 데이터에 따르면 엘리글루스타트는 임상 효능에 있어서 효소 보충 요법에 비열등성을 보인다. 장기 결과에 대한 추가 연구가 필요하지만, 엘리글루스타트의 승인은 해당 1형 고셔병 성인 환자들에게 경구 치료제라는 새로운 선택을 가능하게 하였다. 향후 국내에서 엘리글루스타트가 처방 가능해 지면, 각 환자 마다 철저한 평가를 통해 치료법을 선택할 수 있도록 해야 할 것이다. 나아가, 국내 1형 고셔병 환자들을 위해 엘리글루스타트의 사용에 관한 임상적 지침 또한 조만간 개발될 필요가 있다.

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Relationship between RNA- and Protein-Synthesis and Cell Wall Acidification in Auxin-Mediated Elongation of Sunflower Hypocotyls (해바라기 하배축의 오옥신 유도 신장에서 RNA 및 단백질의 합성과 세포벽 산성화의 관계)

  • 조형택
    • Journal of Plant Biology
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    • v.35 no.2
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    • pp.107-116
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    • 1992
  • The roles of RNA- and protein-synthesis and $H^{+}$ excretion in 1AA ($10\;\mu\textrm{M}$)-induced elongation were investigated using abraded hypocotyl segments of sunflower (Helianthus annuus L.). The response of elongation initiated about 13 min after IAA treatment. Removal of cuticle, acting as diffusion barrier for inhibitors, by mechanical abrasion of hypocotyl segments enhanced the effect of inhibitors markedly, but the degree of abrasion for the saturated effect of inhibition was different among inhibitors. The elongation induced by 1M was completely inhibited when cycloheximide ($10\;\mu\textrm{M}$) was applied to abraded hypocotyl segments as shortly as 4 min before the onset of the growth response (= 10 min after administration of IAA). Cordycepin ($200\;\mu\textrm{M}$) prevented completely 1AA-induced elongation when applied as shortly as 19 min before the onset of the growth response (=5 min before administration of 1AA). Vanadate (1 mM) inhibited both lAA-induced elongation and medium acidification via lAA-induced $H^{+}$ excretion to apoplast. Cycloheximide and cordycepin also prevented lAA-induced $H^{+}$ excretion strongly. However, inhibition by cycloheximide of lAA-induced elongation was not alleviated by acidifying the cell wall to pH 4.5. The results indicate that, a few minutes before the initiation of growih, protein synthesis is demanded for the initiation of 1AA-induced elongation and the $H^{+}$ excretion to cell wall, and that the H+ excretion, even though it may be necessary for elongation, does not seem to bring about acid growth simply through acidifying cell wall.l wall.

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Caulerpa okamurae ethanol extract improves the glucose metabolism and insulin sensitivity in vitro and in vivo (옥덩굴 에탄올 추출물의 당 대사 및 인슐린 민감성 개선효과)

  • Park, Chul-Min;Thakuri, Laxmi Sen;Rhyu, Dong-Young
    • Journal of Applied Biological Chemistry
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    • v.64 no.1
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    • pp.89-96
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    • 2021
  • The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

The Effects of 5-benzylacyclouridine on the Cytotoxicities of Fluorinated Pyrimidine Antimetabolic Agents in L5178Y Cells (L5187Y 세포에 대한 불화피리미딘 대사억제제 독성에 관한 Benzylacyclouridine의 영향)

  • Lee, Kang-Hyun;Cha, Sung-Man
    • The Korean Journal of Pharmacology
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    • v.26 no.1
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    • pp.91-100
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    • 1990
  • The benzylacycoluridines (BAU and BBAU) are potent and specific inhibitors of uridine phosphorylase (UrdPase). In contrast to the report that benzylacyclouridines potentiated 5-fluoro-2'-deoxyuridine (FdUrd) cytotoxicity against human solid tumor cells (Cancer Res., 44:1852, 1984), continuous exposure of mouse lymphoma L5178Y cells, to FdURd, 5-fluorouridine (FUrd), 5'-deoxy-5-fluorouridine (5'-dFUrd), or 5-fluorouracil (FUra) showed no potentiation of cytotoxicity by benzylacyclouridines. In fact, under the conditions employed, benzylacycoluridines protected the cells from the cytotoxicity of FdUrd, FUrd, or 5'-dFUrd, but not FUra in a dose dependent manner. Intraperitoneal coadministration of BAU or BBAU and a 5-fluorinated pyrimidine (i.e., FdUrd, FUrd, or FUra), to mice bearing L5178Y cells also did not significantly increase the life span compared to those treated with the antimetabolites alone. Anabolism of these nucleosides through the sequential action of UrdPase and orotate phosphoribosyltransferase (OPRTase), inhibition of nucleoside transport by benzylacyclouridines, or both could be responsible for the ineffectiveness of UrdPase inhibitors to potentiate the antineoplastic activity of fluoropvrimidines in L5178Y cells.

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