• Title/Summary/Keyword: Transporters

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Metabolism and drug interactions of Korean ginseng based on the pharmacokinetic properties of ginsenosides: Current status and future perspectives

  • Jong Dae Park
    • Journal of Ginseng Research
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    • v.48 no.3
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    • pp.253-265
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    • 2024
  • Orally administered ginsenosides, the major active components of ginseng, have been shown to be biotransformed into a number of metabolites by gastric juice, digestive and bacterial enzymes in the gastrointestinal tract and also in the liver. Attention is brought to pharmacokinetic studies of ginseng that need further clarification to better understand the safety and possible active mechanism for clinical application. Experimental results demonstrated that ginsenoside metabolites play an important role in the pharmacokinetic properties such as drug metabolizing enzymes and drug transporters, thereby can be applied as a metabolic modulator. Very few are known on the possibility of the consistency of detected ginsenosides with real active metabolites if taken the recommended dose of ginseng, but they have been found to act on the pharmacokinetic key factors in any clinical trial, affecting oral bioavailability. Since ginseng is increasingly being taken in a manner more often associated with prescription medicines, ginseng and drug interactions have been also reviewed. Considering the extensive oral administration of ginseng, the aim of this review is to provide a comprehensive overview and perspectives of recent studies on the pharmacokinetic properties of ginsenosides such as deglycosylation, absorption, metabolizing enzymes and transporters, together with ginsenoside and drug interactions.

The Mechanism of Iron Transport after Intratracheal Instillation of Iron in Rats (랏트의 기관내 Fe 노출후 Fe 이동에 대한 연구)

  • Kwon, Min;Choi, Byung-Sun;Park, Eon-Sub;Chung, Nam-Hyun;Park, Sung-Jo;Lim, Young;Park, Jung-Duck
    • Journal of Preventive Medicine and Public Health
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    • v.37 no.4
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    • pp.329-336
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    • 2004
  • Objectives : Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. Methods : Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. Results : The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. Conclusions : DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.

The effect of protease on growth performance, nutrient digestibility, and expression of growth-related genes and amino acid transporters in broilers

  • Park, Jae Hong;Lee, Sang In;Kim, In Ho
    • Journal of Animal Science and Technology
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    • v.62 no.5
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    • pp.614-627
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    • 2020
  • During the course of this trial, our team assessed the influence of protease upon the growth performance, the nutrient digestibility, and the expression of growth-related genes and amino acid transporters within the liver, muscle, and small intestines of broilers. During the first step, our team allocated 600 broilers into four dietary treatments for a period of 35 days in order to measure the growth performance and nutrient digestibility of the broilers selected. The separate treatments contained 10 replicates (15 birds per replicate). The treatments were composed of: 1) CON, basal diet; 2) T1, basal diet + 0.03% protease; 3) T2, basal diet + 0.06% protease; and 4) T3, basal diet + 0.09% protease. Next, the broiler chick sample tissue was harvested from the CON and T3 groups in order to conduct gene expression analysis following the feeding trials the broilers underwent. Our team discovered that the broilers fed protease diets possessed increased body weight and an average daily gain, but conversely, had lower feed conversion ratios when their dietary protease levels increased from 0% to 0.09% (p < 0.05). Additionally, significant linear improvements were identified among the nutrient digestibility of dry matter, crude protein, energy, and amino acids within broilers supplied with protease diets when contrasted and compared with broilers supplied with the basal diet (p < 0.05). In addition, the gene expression of the genes IGF1, IGF2, GH, and LEP in the liver, and the genes MYOD1 and MYOG in the breast muscles, was significantly increased after broilers were fed with a protease diet as compared to broilers that subsisted on a basal diet (p < 0.05). Protease supplementation also raised the expression levels within these amino acid transporters: SCL6A19, SLC7A1, SLC7A7, SLC7A2, SLC7A6, SLC7A9, and SLC15A1, located in the small intestine, when compared to the basal diet (p < 0.05). Our results suggest that protease supplementation in their diet improved the growth performance of broilers via an increase in the expression growth-related genes within broiler liver and muscle tissue. In addition, protease supplementation enhanced broiler digestibility via the upregulation of amino acid transporter expression within the small intestine.

Responsibility allocation by awareness of parties on dangerous goods in maritime transport (국제해상운송에서 위험화물 인지에 따른 당사자의 책임 분배에 관한 연구)

  • Lee, Yang-Kee;Choi, Ji-Ho;Shin, Hak-Sung
    • International Commerce and Information Review
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    • v.16 no.4
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    • pp.125-150
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    • 2014
  • The number of dangerous goods are increasing in maritime transport. As a result, a number of nations and international organizations are establishing or amending the rules of dangerous goods. There is necessarily the transport of dangerous goods like fuel and the importance of the definition and scope of the goods is increased. In addition, the responsibility between the parties is different with the notification of the goods and its awareness of transporters. In particular, responsible clauses of the transport rule show antithetical concepts between the scope of immunity and the responsibility of a shipper concerned with wether transporters aware. This research performs two works. First, this research analyzes the definitions and scope of dangerous goods through prior research. Second, this research suggests the necessary of united interpretation of the articles through a comparative analysis on judical decisions concerned with awareness of transporters to dangerous goods. Dangerous goods have a distinctive feature and that is why responsibility and immunity between parties should be differently interpreted with general rules. Parties have duty concerned with faults on general goods and the scope of duty between parties can be specifically made. However, if there is no specific articles concerned with responsibility between parties to dangerous goods, they could confuse the responsibility on duties concerned with risk. Therefore, this research suggests solutions and necessary of the united criteria for the articles to dangerous goods through analyzing precedent cases.

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(γ-Aminobutyric Acid Transporter 2 Binds to the PDZ Domain of Mammalian Lin-7 ((γ-Aminobutyric acid transporter 2와 mammalian Lin-7의 PDZ결합)

  • Seog, Dae-Hyun;Moon, II-Soo
    • Journal of Life Science
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    • v.18 no.7
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    • pp.940-946
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    • 2008
  • Neurotransmitter transporters, which remove neurotransmittesr from the synaptic cleft, are regulated by second messenger such as protein kinases and binding proteins. Neuronal ${\gamma}-aminobutyric$ acid transporters (GATs) are responsible for removing the inhibitory neurotransmitter ${\gamma}-aminobutyric$ acid (GABA) from the synaptic cleft. ${\gamma}-aminobutyric$ acid transporters 2 (GAT2/BGT1) is involved in regulating neurotransmitter recycling, but the mechanism how they are stabilized and regulated by the specific binding protein has not yet been elucidated. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the C-terminal region of GAT2 and found a specific interaction with the mammalian LIN-7b (MALS-2). MALS-2 protein bound to the tail region of GAT2 but not to other GAT members in the yeast two-hybrid assay. The "T-X-L" motif at the C-terminal end of GAT2 is essential for interaction with MALS-2. In addition, this protein showed specific interactions in the glutathione S-transferase (GST) pull-down assay. An antibody to GAT2 specifically co-immunoprecipitated MALS associated with GAT2 from mouse brain extracts. These results suggest that MALS may stabilize GAT2 in brain.

Changes in expression of monocarboxylate transporters, heat shock proteins and meat quality of Large White Yorkshire and Ghungroo pigs during hot summer period

  • Parkunan, Thulasiraman;Das, Arun K.;Banerjee, Dipak;Mohanty, Niharika;Paul, Avishek;Nanda, P.K.;Biswas, TK;Naskar, Syamal;Bag, Sadhan;Sarkar, Mihir;Mohan, Narayana H.;Das, Bikash Chandra
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.2
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    • pp.246-253
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    • 2017
  • Objective: Present study explores the effect of hot summer period on the glycolytic rate of early post-mortem meat quality of Ghungroo and Large White Yorkshire (LWY) pig and comparative adaptability to high temperature between above breeds by shifting the expression of stress related genes like mono-carboxylate transporters (MCTs) and heat shock proteins (HSPs). Methods: Healthy pigs of two different breeds, viz., LYW and Ghungroo (20 from each) were maintained during hot summer period (May to June) with a mean temperature of about $38^{\circ}C$. The pigs were slaughtered and meat samples from the longissimus dorsi (LD) muscles were analyzed for pH, glycogen and lactate content and mRNA expression. Following 24 h of chilling, LD muscle was also taken from the carcasses to evaluate protein solubility and different meat quality measurements. Results: LWY exhibited significantly (p<0.01) higher plasma cortisol and lactate dehydrogenase concentration than Ghungroo indicating their higher sensitivity to high temperature. LD muscle from LWY pigs revealed lower initial and ultimate pH values and higher drip loss compared to Ghungroo, indicating a faster rate of pH fall. LD muscle of Ghungroo had significantly lower lactate content at 45 min postmortem indicating normal postmortem glycolysis and much slower glycolytic rate at early postmortem. LD muscle of LWY showed rapid postmortem glycolysis, higher drip loss and higher degrees of protein denaturation. Ghungroo exhibited slightly better water holding capacity, lower cooking loss and higher protein solubility. All HSPs (HSP27, HSP70, and HSP90) and MCTs (MCT1, MCT2, and MCT4) in the LD muscle of pigs inclined to increase more in Ghungroo than LWY when exposed to high temperature. Conclusion: Effect of high temperature on the variation of HSPs and MCTs may play a crucial role in thermal tolerance and adaptation to different climatic conditions, pH regulation, muscle acidification, drip loss, protein denaturation and also in postmortem meat quality development.

Mechanism of Growth Inhibition by BCH in HEp2 Human Head and Neck Squamous Cell Carcinoma (사람 두경부 편평세포암종 HEp2 세포에서 BCH에 의한 세포성장 억제기전)

  • Choi, Bong-Kyu;Jung, Kyu-Yong;Cho, Seon-Ho;Kim, Chun-Sung;Kim, Do-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.5
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    • pp.555-560
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    • 2008
  • Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the $Na^+$-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed in cancer cells to support their continuous growth and proliferation. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is a model compound for the study of amino acid transporter as a system L selective inhibitor. We have examined the effect and mechanism of BCH on cell growth suppression in HEp2 human head and neck squamous cell carcinoma. The BCH inhibited the L-leucine transport in a concentration-dependent manner with a $IC_{50}$ value of $51.2{\pm}3.8{\mu}M$ in HEp2 cells. The growth of HEp2 cells was inhibited by BCH in the timeand concentration-dependent manners. The formation of DNA ladder was not observed with BCH treatment in the cells. Furthermore, the proteolytic processing of caspase-3 and caspase-7 in the cells were not detected by BCH treatment. These results suggest that the BCH inhibits the growth of HEp2 human head and neck squamous cell carcinoma through the intracellular depletion of neutral amino acids for cell growth without apoptotic processing.

A Study on the Radiation Dose Managements in the Nuclear Medicine Department (핵의학과에서 방사선 피폭관리 실태에 대한 조사 연구)

  • Lim, Chang-Seon;Kim, Se-Heon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.10 no.7
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    • pp.1760-1765
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    • 2009
  • After administration of a radiopharmaceutical, the patient remains radioactive for hours or even days, representing a source of potential radiation exposure. Thus, including the personnel who are occupationally exposed to ionizing radiation, radiation exposure must be managed for members of the public, in particular for people accompanying patients. In this study we investigated radiation exposure dose management in the nuclear medicine departments at seven general hospitals. Two of them had no radiation safety considerations for patient transporters, sanitation workers and the like. And they all were careless of radioprotection for people accompanying patients. The average dose rate to people accompanying patients from radioactive patients just before a bone scan was 25.60 ${\mu}$Sv h-1. This is higher than 20 ${\mu}$Sv $h^{-1}$which is the annual public dose limit for temporary use. Therefore radiation dose measurement and risk assessment of patient transporters, sanitation workers and the like should be performed. And the nuclear medicine technologist should provide advices on the radiation safety to patient transporters, sanitation workers, people accompanying patients and so on. To ensure the radiation safety for people accompanying patients, it is required to restrict the patient's access to his relatives, friends and other patients or isolate patients.

A Novel ABC Transporter Gene ABC2 Involved in Multidrug Susceptibility but not Pathogenicity in Rice Blast Fungus, Magnaporthe grisea

  • Lee, Young-Jin;Kyosuke Yamamoto;Hiroshi Hamamoto;Ryoji Nakaune;Tadaaki Hibi
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.21-22
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    • 2003
  • Fungicide treatment is the most important method for the control of plant diseases caused by phytopathogenic fungi. But fungicide resistant strains have appeared in many phytopathogenic fungi. Until now, molecular mechanisms of fungicide resistance such as mutation of target protein, overproduction of target enzyme and detoxification of fungicide have been designated. Recently, it was demonstrated that active efflux of fungicides mediated by ATP-binding cassette (ABC) transporters also contributes to fungicide resistance in several filamentous fungi, such as Aspergillus nidulans, Penicillium digitatum and Botrytis cinerea.(중략)

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Human Vesicular Glutamate Transporters Functionally Complement EAT-4 in C. elegans

  • Lee, Dukgyu;Jung, Sunki;Ryu, Jungmin;Ahnn, Joohong;Ha, Ilho
    • Molecules and Cells
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    • v.25 no.1
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    • pp.50-54
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    • 2008
  • The vesicular glutamate transporter (VGLUT) transports glutamate into pre-synaptic vesicles. Three isoforms of VGLUT have been identified in humans, but their functional differences remain largely unknown. EAT-4 is the only homologue of human VGLUT in C. elegans. Here we report that mutants of eat-4 exhibit hyperforaging behavior and that each of the isoforms of human VGLUT functionally rescues the defects in eat-4 worms.