• 제목/요약/키워드: Efflux transport

검색결과 67건 처리시간 0.02초

Plasmid-Mediated Arsenical and Antimonial Resistance Determinants (ars) of Pseudomonas sp. KM20

  • Yoon, Kyung-Pyo
    • Journal of Microbiology and Biotechnology
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    • 제12권1호
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    • pp.31-38
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    • 2002
  • Bacteria have evolved various types of resistance mechanism to toxic heavy metals, such as arsenic and antimony. An arsenical and antimonial resistant bacterium was isolated from a shallow creek draining a coal-mining area near Taebaek City, in Kangwon-Do, Korea. The isolated bacterium was identified and named as Pseudomonas sp. KM20 after biochemical and physiological studies were conducted. A plasmid was identified and its function was studied. Original cells harboring the plasmid were able to grow in the presence of 15 mM sodium arsenite, while the plasmid-cured (plasmidless) strain was sensitive to as little as 0.5 mM sodium arsenate. These results indicated that the plasmid of Pseudomonas sp. KM20 does indeed encode the arsenic resistance determinant. In growth experiments, prior exposure to 0.1 mM arsenate allowed immediate growth when they were challenged with 5 mM arsenate, 5 mM arsenite, or 0.1 mM antimonite. These results suggested that the arsenate, arsenite, and antimonite resistance determinants of Pseudomonas sp. KM20 plasmid were indeed inducible. When induced, plasmid-bearing resistance cells showed a decreased accumulation $of\;73^As$ and showed an enhanced efflux $of\;^73As$. These results suggested that plasmid encoded a transport system that extruded the toxic metalloids, resulting in the lowering of the intracellular concentration of toxic oxyanion. In a Southern blot study, hybridization with an E. coli R773 arsA-specific probe strongly suggested the absence of an arsA cistron in the plasmid-associated arsenical and antimonial resistance determinant of Pseudomonas sp. KM20.

Incidence of Erythromycin Resistance Genes, erm(B) and mef(A), in Streptococci Isolated from Dental Plaques of Koreans

  • Kim, Yeon-Hee;Lee, Si-Young
    • International Journal of Oral Biology
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    • 제38권2호
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    • pp.61-65
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    • 2013
  • Erythromycin is a macrolide antibiotic and inhibits bacterial protein synthesis by stimulating the dissociation of the peptidyl-tRNA molecule from the ribosomes during elongation. The use of macrolides has increased dramatically over the last few years and has led to an increase in bacterial resistance to these antibiotics. Bacterial resistance to erythromycin is generally conferred by the ribosome methylation and/or transport (efflux) protein genes. Among the identified erythromycin-resistant genes, erm(B) (erythromycin methylation) and mef(A) (macrolide efflux) are generally detectable in erythromycin-resistant streptococcal species. The distribution of these genes in oral streptococcal isolates has been reported in studies from other countries but has not been previously examined in a Korean study. We here examined by PCR the presence of erm(B) and mef(A) in oral streptococci isolated from Korean dental plaques. Among the 57 erythromycin-resistant strains tested, 64.9% harbored erm(B) whereas 40.4% were positive for mef(A). Eleven isolates had both the erm(B) and mef(A) genes. Twenty six isolates had only erm(B) and 12 isolates had only mef(A). Eight of the 57 strains examined were negative for both genes.

콜레스테롤 식이와 운동이 흰쥐의 체내 지질수준, 혈소판 응집 및 적혈구막 Na 유출에 미치는 영향 (Effects of Cholesterol Diet and Exercise on Plasma and Liver Lipids, Platelet Aggregation and Erythrocyte Na Efflux in Rats)

  • 강민숙;김영표;강영희;강정숙
    • Journal of Nutrition and Health
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    • 제41권5호
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    • pp.381-390
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    • 2008
  • 본 실험은 콜레스테롤식이와 운동수행이란 두 조건을 심순환기 질환의 관련지표로서 혈장 및 간의 지질, 적혈구막의 Na efflux 그리고 혈소판 응집성에 어떠한 영향을 미치는지 조사하였다. 운동에 의해서 체중이 다소 감소하였지만 그렇게 크지는 않았다. 라드를 주 지방원으로 사용한 식이에 0.5% 콜레스테롤첨가는 혈중 콜레스테롤을 2배 이상, 간 콜레스테롤을 8배 이상 증가시켰고 HDL-콜레스테롤을 절반 이하로 떨어뜨렸는데, 특히 운동효과로 예상했던 HDL-콜레스테롤증가는 대조군식이나 콜레스테롤식이에서 나타나지 않았다. 혈중 중성지방은 콜레스테롤 식이군에서 오히려 감소하였고 간의 경우 지방 축척으로 인해 간의 크 기뿐만 아니라 간의 중성지방은 현저히 증가되었다. 체액량 조절 및 혈압과 관계에서 조사된 적혈구의 Na efflux는 Na-K ATPase가 콜레스테롤 식이에 의해 그 활성을 감소되었고 운동이 이를 다소 회복시키는 경향을 보였다. 혈압과의 상관성이 높다고 알려진 Na passive leak은 콜레스테롤과 운동이 각각 독립적으로 증가시키는 요인으로 작용하여 콜레스테롤-운동군이 대조군식이-비운동군에 비해 현저히 증가된 것으로 나타났다. 총 Na efflux는 실험군 간에 큰 차이가 없었고 intracellular Na와의 상관성도 보이질 않았다. 혈소판응집성에 있어서 콜레스테롤식이가 혈소판 응집을 증가시키고 특히 운동이 초기응집을 증가시키는 경향을 보였다. 혈장 GOT 및 GPT수치는 콜레스테롤식이로 인해 현저히 증가됨으로서 간의 병리적 상태를 잘 반영하였고 운동에 의해 감소됨으로서 운동수행이 술이나 고지방식으로 인한 지방간을 호전시켜 줄 수 있으리라 기대할 수 있다. 고지혈증이나 고혈압 환자에 있어서 비약물적 요법으로 식이나 운동을 통한 치료나 예방의 가능성을 규명하기 위한 실험의 결과로서 특히 운동에 대해 일관되고 가시적인 효과가 미흡한 것은 6주간의 짧은 실험기간을 생각할 수 있는데 혈청 지질, Na flux 및 체액, 혈소판 응집성 등 심순환기 질환의 예방에 도움이 되는 운동의 형태나 강도 혹은 지속 기간에 대한 더 많은 연구가 필요하리라 생각된다.

기능적 영상술을 이용한 다약제 내성의 체내 진단 (Functional Imaging of the Multidrug Resistance In Vivo)

  • 이재태
    • 대한핵의학회:학술대회논문집
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    • 대한핵의학회 2001년도 제40차 춘계학술대회 및 연수교육
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    • pp.66-75
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    • 2001
  • Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

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가토 신피질 절편에서 Uric Acid 이동 (Accumulation of Uric Acid in Rabbit Kidney Cortical Slices)

  • 이성태;임채준;우재석;김용근
    • The Korean Journal of Physiology
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    • 제21권2호
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    • pp.283-289
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    • 1987
  • Uric acid transport across the basolateral membrane of renal proximal tubules was studied in rabbit kidney cortical slices. Uric acid uptake was greater under $O_2$ atmosphere compared to under $N_2$ atmosphere, and was increased with $Na^{2+}$ concentration in incubation medium. Uric acid inhibited PAH uptake but not TEA uptake and did trans-stimulated PAH efflux. PAH also inhibited uric acid uptake. Uric acid uptake was inhibited by harmaline, ouabin, SITS, DIDS and pyrazinoic acid. The inhibition of PAH uptake by these inhibitors also was reasonably comparable to that of uric acid uptake. These results suggest that uric acid was transported across the basolateral membrane of renal tubule by a carrier-mediated process which was by a common transport system with PAH in rabbit.

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The Molecular Functions of RalBP1 in Lung Cancer

  • Lee, Seunghyung
    • 대한의생명과학회지
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    • 제20권2호
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    • pp.49-55
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    • 2014
  • RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cells including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lung cancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increase sensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1 blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancer cells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on its domain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sites for multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recently shown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discuss the cellular and physiological functions of RalBP1 in normal and lung cancer cells.

Functional characterization of Clonorchis sinensis choline transporter

  • Jeong Yeon Won;Johnsy Mary Louis;Eui Sun Roh;Seok Ho Cha;Jin-Hee Han
    • Parasites, Hosts and Diseases
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    • 제61권4호
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    • pp.428-438
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    • 2023
  • Clonorchis sinensis is commonly found in East Asian countries. Clonorchiasis is prevalent in these countries and can lead to various clinical symptoms. In this study, we used overlap extension polymerase chain reaction (PCR) and the Xenopus laevis oocyte expression system to isolate a cDNA encoding the choline transporter of C. sinensis (CsChT). We subsequently characterized recombinant CsChT. Expression of CsChT in X. laevis oocytes enabled efficient transport of radiolabeled choline, with no detectable uptake of arginine, α-ketoglutarate, p-aminohippurate, taurocholate, and estrone sulfate. Influx and efflux experiments showed that CsChT-mediated choline uptake was time- and sodium-dependent, with no exchange properties. Concentration-dependent analyses of revealed saturable kinetics consistent with the Michaelis-Menten equation, while nonlinear regression analyses revealed a Km value of 8.3 µM and a Vmax of 61.0 pmol/oocyte/h. These findings contribute to widen our understanding of CsChT transport properties and the cascade of choline metabolisms within C. sinensis.

Effect of Cisplatin on Sodium-Dependent Hexose Transport in LLC-$PK_1$ Renal Epithelial Cells

  • Lee, Suk-Kyu;Kim, Jee-Yeun;Yu, Tai-Hyun;Kim, Kyoung-Ryong;Kim, Kwang-Hyuk;Park, Yang-Saeng
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권1호
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    • pp.35-43
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    • 1997
  • Cis-dichlorodiammine platin${\mu}M$II (Cisplatin), an effective chemotherapeutic agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin on the renal proximal tubular transport system, LLC-$PK_1$ cell line was selected as a cell model and the sugar transport activity was evaluated during a course of cisplatin treatment. Cells grown to confluence were treated with cisplatin for 60 min, washed, and then incubated for up to 5 days. At appropriate intervals, cells were tested for sugar transport activity using ${\alpha}-methyl-D-[^{14}C]glucopyranoside$ (AMG) as a model substrate. In cells treated with 100 ${\mu}M$ cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 ${\mu}M$, but it decreased markedly with 150 and 200 ${\mu}M$. In cisplatin-treated cells, the $Na^+$ -dependent AMG uptake was drastically inhibited with no change in the $Na^+$ -independent uptake. Kinetic analysis indicated that Vmax was suppressed, but Km was not altered. The $Na^+$ -dependent phlorizin binding was also decreased in cisplatin-treated cells. However, the AMG efflux from preloaded cells was not apparently retarded by cisplatin treatment. These data indicate that the cisplatin treatment impairs $Na^+$ -hexose cotransporters in LLC-$PK_1$ cells and suggest strongly that defects in transporter function at the luminal plasma membrane of the proximal tubular cells constitute an important pathogenic mechanism of cisplatin nephrotoxicity.

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Recent Updates on Acetaminophen Hepatotoxicity: The Role of Nrf2 in Hepatoprotection

  • Gum, Sang Il;Cho, Min Kyung
    • Toxicological Research
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    • 제29권3호
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    • pp.165-172
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    • 2013
  • Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

Self-Diffusion of THO within Tactic Poly(2-hydroxyethyl methacrylate) Membranes

  • Kim, Hye-Kyeong;Jhon, Mu-Shik
    • Bulletin of the Korean Chemical Society
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    • 제4권3호
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    • pp.128-132
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    • 1983
  • The self-diffusion experiment of water was performed across two series of tactic poly(2-hydroxyethyl methacrylate), P(HEMA) membranes prepared by crosslinking with various amount of hexamethylene diisocyanate (HMDIC). The tagging material was tritium hydroxide (THO) and the efflux of THO was counted on a Liquid Scintillation Counter. The transport data of THO show that the permeability decreases as the amount of HMDIC increased from 2.5 to 10 mole % and the self-diffusions coefficient shows a parallel trend with it. The diffusivity data was discussed in terms of the change of water structural orderliness within membranes. Using the relation between viscosities and diffusivities derived from Eyring's absolute rate theory, the corresponding viscosities of water within two series of tactic P(HEMA) membranes were obtained. From this, it is seen that the viscosity of water within tactic P(HEMA) membranes may have the same values with those of supercooling water whose temperature ranges from -28 to -$36^{\circ}C.$.