• 제목/요약/키워드: selective uptake

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Effect of a New Hepatoprotective Agent, YH-439, on the Hepatobiliary Transport of Organic Cations (OCs): Selective Inhibition of Sinusoidal OCs Uptake without Influencing Glucose Uptake and Canalicular OCs Excretion

  • Hong Soon Sun;Li Hong;Choi Min Koo;Chung Suk Jae;Shim Chang Koo
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.330-334
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    • 2005
  • The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 $\mu$mol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance ($CL_b$) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane ($CL_{exc}$) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent V$_{max}$ and $CL_{linear}$, but the $K_m$ for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

Removal, Recovery, and Process Development of Heavy Metal by Immobilized Biomass Methods (미생물 고정화법에 의한 중금속 제거, 회수 및 공정개발)

  • Ahn, Kab-Hwan;Shin, Yong-Kook;Suh, Kuen-Hack
    • Journal of Environmental Science International
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    • v.6 no.1
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    • pp.61-67
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    • 1997
  • Heavy metal adsorption by microbial cells is an alternative to conventional methods of heavy metal removal and recovery from metal-bearing wastewater The waste Sac-chuomyces cerevisiae is an inexpensive, relatively available source of biomass for heavy metal biosorption. Biosorption was investigated by free and immobilized-S. cerevisiae. The order of biosorption capacity was Pb>Cu>Cd with batch system. The biosorption parameters had been determined for Pb with free , cells according to the Freundlich and Langmuir model. It was found that the data fitted reasonably well to the Freundlich model. The selective uptake of immobilized-S. cerevisiae was observed when all the metal ions were dissolved in a mixed metals solution(Pb, Cu, Cr and Cd). The biosorption of mixed metals solution by immobilized-cell was studied in packed bed reactor. The Pb uptake was Investigated in particular, as it represents one of the most widely distributed heavy metals in water. We also tested the desorption of Pb from immobilized-cell by us- ing HCI, $H_2SO_4$ and EDTA.

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JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells

  • Choi, Dae Woo;Kim, Do Kyung;Kanai, Yoshikatsu;Wempe, Michael F.;Endou, Hitoshi;Kim, Jong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.599-607
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    • 2017
  • Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

Effect of Nitric Oxide on the Sinusoidal Uptake of Organic Cations and Anions by Isolated Hepatocytes

  • Song, Im-Sook;Lee, In-Kyoung;Chung, Suk-Jae;Kim, Sang-Geon;Lee, Myung-Gull;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.984-988
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    • 2002
  • The issue of whether or not the presence NOx (NO and oxidized metabolites) in the hepatocytes at pathological levels affects the functional activity of transport systems within the sinusoidal membrane was investigated. For this purpose, the effect of the pretreatment of isolated hepatocytes with sodium nitroprusside (SNP), a spontaneous NO donor, on the sinusoidal uptake of tributylmethylammonium (TBuMA) and triethylmethyl ammonium (TEMA), representative substrates of the organic cation transporter (OCT), and taurocholate, a representative substrate of the $Na^+$/taurocholate cotransporting polypeptide (NTCP), was measured. The uptake of TBuMA and TEMA was not affected by the pretreatment, as demonstrated by the nearly identical kinetic parameters for the uptake ($i.e., V_{max}, K_{m} and CL_{linear}$). The uptake of mannitol into hepatocytes was not affected, demonstrating that the membrane integrity remained constant, irregardless of the SNP prutreatment. On the contrary, the uptake of taurocholate was significantly inhibited by the pretreatment, resulting in a significant decrease in V_{max}$, thus providing a clear demonstration that NOx preferentially affects the function of NTCP rather than OCT on the sinusoidal membrane. A direct interaction between NOx and NTCP or a decrease in $Na^+/K^+$ ATPase activity as the result of SNP pretreatment might be responsible for this selective effect of NOx.

Hydrogen Spillover Kinetics - I. Effect of Surface Morphology on [$Pt/MoO_{3}$] Catalyst (수소 spillover 속도론 - I. $Pt/MoO_{3}$ 촉매의 표면 형상 변화)

  • Kim Jin Gul;Kim Seong-Soo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.5 no.6
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    • pp.491-494
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    • 2004
  • [ $H_2$ ] uptake into $Pt/MoO_{3}$ was enhanced with an increased calcination temperature. Selective CO pulse chemisorption demonstrated that free Pt surface area was decreased as calcination temperature was increased. Characteristic techniques were dedicated to elucidate the closer contact at adlineation sites between Pt and $MoO_3$ substrates. Calcination resulted in supplying the hydrogen access into more $MoO_3$ particles and controlling the kinetics of hydrogen uptake.

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Soil Properties Affecting the Adsorption of Lead (Pb의 흡착에 영향을 미치는 토양의 특성)

  • 박상원
    • Journal of Environmental Science International
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    • v.8 no.1
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    • pp.69-74
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    • 1999
  • Soil properties which affect the retention of Pb(I) were investigated in the laboratory. It was determined, through selective removal, that organic matter and Fe-oxides are of lesser importance in influencing Pb retention than are soil clay minerals. The following trend : clays > organic matter > Fe-oxides represents the relative importance of each constituent in the adsorption of Pb by soils. The consistently greater Pb uptake by surface over subsurface samples was apparently due to differences in organic matter content, inasmuch as organic matter removal from both resulted in similar adsorption characteristics. All five soils stooled exhibited a pH-dependent trend of adsorption. The extent of Pb adsorption was least at low pH values(4~5), was maximum in the neutral pH range, and leveled off or diminished under more alkaline conditions. There was no strong correlation between Pb uptake and soil cation exchange capacity as routinely measured by the NH$_4$OAc method. A knowledge of clay mineralogy in conjunction with soil pH is suggested as being the most reliable guide to predicting Pb retention by soils.

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Functionalization of polyethylene by graft copolymerization for separation processes

  • Kaur, Inderjeet;Gupta, Nitika;Kumari, Vandna
    • Advances in materials Research
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    • v.2 no.1
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    • pp.15-36
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    • 2013
  • Incorporation of polar functional moieties into polyethylene (PE) film has been achieved by graft copolymerization of polar monomers such as methacrylic acid (MAAc) and acrylamide (AAm) on to PE film, preirradiated with ${\gamma}$-rays from $^{60}Co$ source, using benzoyl peroxide (BPO) as initiator in aqueous medium. Percentage of grafting of MAAc and AAm was determined as a function of irradiation dose, monomer and initiator concentration, temperature, reaction time and amount of water. Maximum percentage of grafting of MAAc (1453%) and AAm (21.28%) was obtained at [MAAc] = $235.3{\times}10^{-2}$ mol/L, [AAm] = $23.4{\times}10^{-2}$ mol/L, [BPO] = $5.5{\times}10^{-2}$ mol/L and $16.5{\times}10^{-2}$ mol/L at $80^{\circ}C$, $90^{\circ}C$ in 180 min and 90 min respectively. The grafted PE films were characterized by FTIR, Thermogravimetric analysis (TGA) Scanning Electron Micrography (SEM) and X-ray diffraction methods. Some selective properties of grafted films such as swelling behavior, ion and metal uptake have been carried out. The biodegradation studies of the grafted PE films have also been investigated. The grafted films developed superior swelling behavior with maximum swelling (480%) in water as compared to pristine PE (13.55%), better thermal stability and ion and metal uptake studies showed promising results that can be effectively used for desalination of brackish water and separation of metals from the industrial effluents.

Functional Experessions of Endogenous Dipeptide Transporter and Exogenous Proton/Peptide Cotransporter in Xenopus Oocytes

  • Oh, Doo-Man;Amidon-Gordon-L.;Sadee-Wolfgang
    • Archives of Pharmacal Research
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    • v.18 no.1
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    • pp.12-17
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    • 1995
  • It is essential to clone the preptide transporter in order to obtain better understanding of its molecular structure, regulation, and substrate specificity. Characteristics of an endogenous peptide transporter in oocytes were studied along with expression of an exogenous protor/peptide cotransporter from rabbit intestine. And further efforts toward cloning the transporter were performed. The presence of an endogenous peptide transporter was detected in Xenopus laevis oocytes by measuring the uptake of $0.25/{mu}M(10{\;}{\mu}Ci/ml)[^3H]$-glycylsarcosine (Gly-Sar) at pH 5.5 with or without inhibitors. Yptake of Gly-Sae in oocytes was significantly inhibited by $25{\mu}M$ glycine nd sarcosine. This result suggests that a selective transporter is involved in the endogneous uptake of dipeptides. Collagenase treatment of oocytes used to strip oocytes from ovarian follicles did not affect the Gly-Sar uptake. Changing pH from 5.5 to 7.5 did not affect the Gly-Sae uptake significantly, suggesting no depedence of the endogenous transporter on a transmembrane proton gradient. An exogenous $H^+/pep-tide$ contransported was expressed after microinjection of polyadenylated messenger ribonucleic acid $[poly(A)^+ -mRNA]$ obtained from rabbit small intestine. The Gly-Sar uptake in mRNA-injected oocytes was 9 times thigher than that in water-injected oocyltes. Thus, frog occytes can be utilized fro expression cloning of the genes encoding intestinal $H^+$peptide contransporters. Size fractionation of mRNA was successfully obtained using this technique.

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Agricultural Methods for Toxicity Alleviation in Metal Contaminated Soils: A Review

  • Arunakumara, Kkiu;Walpola, Buddhi Charana;Yoon, Min-Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.46 no.2
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    • pp.73-80
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    • 2013
  • Due to the fact that possible risk associated with soil-crop-food chain transfer, metal contamination in croplands has become a major topic of wide concern. Accumulation of toxic metals in edible parts of crops grown in contaminated soils has been reported from number of crops including rice, soybean, wheat, maize, and vegetables. Therefore, in order to ensure food safety, measures are needed to be taken in mitigating metal pollution and subsequent uptake by crop plants. Present paper critically reviewed some of the cost effective remediation techniques used in minimizing metal uptake by crops grown in contaminated soils. Liming with different materials such as limestone ($CaCO_3$), burnt lime (CaO), slaked lime [$Ca(OH)_2$], dolomite [$CaMg(CO_3)_2$], and slag ($CaSiO_3$) has been widely used because they could elevate soil pH rendering metals less-bioavailable for plant uptake. Zn fertilization, use of organic amendments, crop rotation and water management are among the other techniques successfully employed in reducing metal uptake by crop plants. However, irrespectively the mitigating measure used, heterogeneous accumulation of metals in different crop species is often reported. The inconsistency might be attributed to the genetic makeup of the crops for selective uptake, their morphological characteristics, position of edible parts on the plants in respect of their distance from roots, crop management practices, the season and to the soil characteristics. However, a sound conclusion in this regard can only be made when more scientific evidence is available on case-specific researches, in particular from long-term field trials which included risks and benefits analysis also for various remediation practices.

Cancer-targeted photothermal therapy using aptamer-conjugated gold nanoparticles

  • Hong, Eun Ji;Kim, Yoon-Seok;Choi, Dae Gun;Shim, Min Suk
    • Journal of Industrial and Engineering Chemistry
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    • v.67
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    • pp.429-436
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    • 2018
  • Targeted intracellular delivery of therapeutic agents is one of the great challenges for cancer treatment. Aptamers that bind to a variety of biological targets have emerged as new targeting moieties with high specificity for targeted cancer therapy. In this study, near-infrared (NIR) light-absorbing hollow gold nanocages (AuNCs) were synthesized and conjugated with AS1411 aptamer to achieve cancer-targeted photothermal therapy. AuNC functionalized with PEG and AS1411 (AS1411-PEG-AuNC) exhibited selective cellular uptake in breast cancer cells due to selective binding of AS1411 to nucleolin, a protein that is over-expressed in cancer cells over normal cells. As a result, AS1411-PEG-AuNC showed cancer-targeted photothermal activity. This study demonstrates that aptamer-conjugated AuNCs are effective tumor-targeting photothermal agents.