• 제목/요약/키워드: Mechanisms of uptake

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악성종양의 포도당 섭취 기전 (Mechanisms of Glucose Uptake in Cancer Tissue)

  • 정준기
    • 대한핵의학회지
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    • 제33권1호
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    • pp.1-10
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    • 1999
  • Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycotytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.

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약물의 간내 이행기전과 알부민의 역할 (Albumin-Mediated Hepatic Uptake of Drugs)

  • 한용해;심창구
    • Journal of Pharmaceutical Investigation
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    • 제20권4호
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    • pp.179-191
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    • 1990
  • A central dogma of pharmacology is that only unbound drug is capable of translocation across biological membrane. Thus, hepatic uptake is assumed to be solely determined by the unbound concentration of the diffusible moiety at the surface of the liver cell. However, an increasing number of experimental observations with xenobiotics that are normally very extensively bound to plasma proteins (>99%) appear to be inconsistent with these assumptions. This suggested that in addition to progressive spontaneous dissociation within the liver sinusoids and space of Disse, direct interactions of the albumin-drug complex at the plasma membrane may facilitate dissociation of the complex. To explain this phenomena. called albumin-mediated uptake, 4 mechanisms have been suggested. The validity of such hypotheses needs to be examined by the further study. Because albumin-mediated uptake has also been observed to occur in other plasma proteins, protein-mediated uptake rather than albumin-mediated uptake seems to be acceptable.

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대마 뿌리 및 줄기 추출물의 포도당 흡수 개선 효과 및 기전에 대한 비교 연구 (A Comparative Study on the Efficacy and Mechanism of Improving Glucose Uptake of Cannabis Root and Stem Extracts)

  • 진혜린;유가람;김혁;조규형;김기현;임동우
    • 한방비만학회지
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    • 제23권2호
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    • pp.51-59
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    • 2023
  • Objectives: Despite the pharmacological potential of the roots and stems of hemp based on literatures, active research has not been conducted for a long time. Comparative experiments were conducted on antioxidant and anti-inflammatory effects and improvement of glucose uptake using Cannabis root and stem extracts. Methods: Antioxidant contents in Cannabis root and stem extracts were examined with total phenolic, tannin, flavonoid assay. Anti-inflammatory properties were tested in lipopolysaccharides-treated RAW264.7 cells. Efficacy of Cannabis root and stem extracts on glucose uptake was investigated using fluorescent glucose analog (2-NBDG) in palmitate-treated HepG2 cells. The mechanism of action on metabolism was examined by western blot. Results: Antioxidant and anti-inflammatory efficacy were greater in stem extracts, but improvements in glucose uptake performed under various conditions were found to be greater in root extracts. It is assumed that Cannabis root extracts exhibited an improvement in glucose uptake through mechanisms such as AMP-activated protein kinase activation, not depending on general antioxidant and anti-inflammatory effects. Conclusions: Further research is needed on the mechanisms and substances that exhibit the anti-diabetic effects of Cannabis roots and stems.

Toxicity of nanoparticles_ challenges and opportunities

  • Ramanathan, Amall
    • Applied Microscopy
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    • 제49권
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    • pp.2.1-2.11
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    • 2019
  • Nanomaterials (NMs) find widespread use in different industries that range from agriculture, food, medicine, pharmaceuticals, and electronics to cosmetics. It is the exceptional properties of these materials at the nanoscale, which make them successful as growth promoters, drug carriers, catalysts, filters and fillers, but a price must be paid via the potential toxity of these materials. The harmful effects of nanoparticles (NPs) to environment, human and animal health needs to be investigated and critically examined, to find appropriate solutions and lower the risks involved in the manufacture and use of these exotic materials. The vast number and complex interaction of NM/NPs with different biological systems implies that there is no universal toxicity mechanism or assessment method. The various challenges need to be overcome and a number of research studies have been conducted during the past decade on different NMs to explore the possible mechanisms of uptake, concentrations/dosage and toxicity levels. This review article examines critically the recent reports in this field to summarize and present opportunities for safer design using case studies from published literature.

Strategies for Improving Potassium Use Efficiency in Plants

  • Shin, Ryoung
    • Molecules and Cells
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    • 제37권8호
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    • pp.575-584
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    • 2014
  • Potassium is a macronutrient that is crucial for healthy plant growth. Potassium availability, however, is often limited in agricultural fields and thus crop yields and quality are reduced. Therefore, improving the efficiency of potassium uptake and transport, as well as its utilization, in plants is important for agricultural sustainability. This review summarizes the current knowledge on the molecular mechanisms involved in potassium uptake and transport in plants, and the molecular response of plants to different levels of potassium availability. Based on this information, four strategies for improving potassium use efficiency in plants are proposed; 1) increased root volume, 2) increasing efficiency of potassium uptake from the soil and translocation in planta, 3) increasing mobility of potassium in soil, and 4) molecular breeding new varieties with greater potassium efficiency through marker assisted selection which will require identification and utilization of potassium associated quantitative trait loci.

Effects of Insulin and IGFs on Phosphate Uptake in Primary Cultured Rabbit Renal Proximal Tubule Cells

  • Han, Ho-Jae;Park, Kwon-Moo
    • The Korean Journal of Physiology
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    • 제30권1호
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    • pp.63-76
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    • 1996
  • The aim of present study was to characterize phosphate uptake and to investigate the mechanism for the insulin and insulin-like growth factor(IGF) stimulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells. Results were as follows : 1. The primary cultured proximal tubule cells had accumulated $6.68{\pm}0.70$ nmole phosphate/mg protein in the presence of 140 mM NaCl and $2.07{\pm}0.17$ nmole phosphate/mg protein in the presence of 140 mM KCl during a 60 minute uptake period. Raising the concentration of extracellular phosphate to 100 mM$(48.33{\pm}1.76\;pmole/mg\;protein/min)$ induced decrease in phosphate uptake compared with that in control cells maintained in 1 mM phosphate$(190.66{\pm}13.01\;pmole/mg\;protein/min)$. Optimal phosphate uptake was observed at pH 6.5 in the presence of 140 mM NaCl. Phosphate uptake at pH 7.2 and pH 7.9 decreased to $83.06{\pm}5.75%\;and\;74.61{\pm}3.29%$ of that of pH 6.5, respectively. 2. Phosphate uptake was inhibited by iodoacetic acid(IAA) or valinomycin treatment $(62.41{\pm}4.40%\;and\;12.80{\pm}1.64%\;of\;that\;of\;control,\;respectively)$. When IAA and valinomycin were added together, phosphate uptake was inhibited to $8.04{\pm}0.61%$ of that of control. Phosphate uptake by the primary proximal tubule cells was significantly reduced by ouabain treatment$(80.27{\pm}6.96%\;of\;that\;of\;control)$. Inhibition of protein and/or RNA synthesis by either cycloheximide or actinomycin D markedly attenuated phosphate uptake. 3. Extracellular CAMP and phorbol 12-myristate 13 acetate(PMA) decreased phosphate uptake in a dose-dependent manner in all experimental conditions. Treatment of cells with pertussis toxin or cholera toxin inhibited phosphate uptake. cAMP concentration between $10^{-6}\;M\;and\;10^{-4}\;M$ significantly inhibited phosphate uptake. Phosphate uptake was blocked to about 25% of that of control at 100 ng/ml PMA. 3-Isobutyl-1-methyl-xanthine(IBMX) inhibited phosphate uptake. However, in the presence of IBMX, the inhibitory effect of exogenous cAMP was not significantly potentiated. Forskolin decreased phosphate transport. Acetylsalicylic acid did not inhibit phosphate uptake. The 1,2-dioctanoyl-sn-glycorol(DAG) and 1-oleoyl-2-acetyl-sn- glycerol(OAG) showed a inhibitory effect. However, staurosporine had no effect on phosphate uptake. When PMA and staurosporine were treated together, inhibition of phosphate uptake was not observed. In conclusion, phosphate uptake is stimulated by high sodium and low phosphate and pH 6.5 in the culture medium. Membrane potential and intracellular energy levels are also an important factor fer phosphate transport. Insulin and IGF-I stimulate phosphate uptake through a mechanisms that involve do novo protein and/or RNA synthesis and decrease of intracellular cAMP level. Also protein kinase C(PKC) is may play a regulatory role in transducing the insulin and IGF-I signal for phosphate transport in primary cultured proximal tubule cells.

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Characteristics of Thiamine Uptake by the BeWo Human Trophoblast Cell Line

  • Keating, Elisa;Lemos, Clara;Azevedo, Isabel;Martel, Fatima
    • BMB Reports
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    • 제39권4호
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    • pp.383-393
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    • 2006
  • Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

Structural basis of Ca2+ uptake by mitochondrial calcium uniporter in mitochondria: a brief review

  • Jiho, Yoo
    • BMB Reports
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    • 제55권11호
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    • pp.528-534
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    • 2022
  • Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca2+ ions for their activity, mitochondria have ion channels to selectively uptake Ca2+ ions from the cytoplasm. The ion channel known to play the most important role in the Ca2+ uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca2+ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca2+ uptake by the MCU holo-complex. Studies of this MCU holo-complex have long been conducted, but we didn't know in detail how mitochondria uptake Ca2+ ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca2+ uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca2+ ions through the MCU holo-complex and how these Ca2+ uptake mechanisms are regulated.

Different mechanisms mediate uptake of lead in a rat glial cell line

  • Cheong, Jae-Hoon;Tan, Tan Blendyl;Kim, Y.B.;Bannon, Bannon Desmond;Olivi, Olivi Luisa;Bressler, Bressler Joseph
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.117.2-117.2
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    • 2003
  • The mechanism by which lead enters glial cells was examined. The uptake of lead reached saturation when assays were performed in buffers at pH 5.5 and 7.4. The Vmax and Km was 2.7 pmoles/mg protein/min and 13.4 M in the buffer at pH 7.4, respectively, whereas the Vmax and Km was 329 fmoles/mg and 8.2 M in the buffer at pH 5.5, respectively. Uptake in a buffer at pH 5.5 but not at pH 7.4 was inhibited by iron. Cells treated with the iron chelator desferoxamine displayed higher levels of the divalent metal transporter mRNA and protein. (omitted)

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초대배양된 토끼 신장 근위세뇨관세포의 성장과 기능분화에 대한 insulin과 IGF의 효과 - Na+ uptake에 대한 IGF-I의 효과 - (Effects of insulin and IGF on growth and functional differentiation in primary cultured rabbit kidney proximal tubule cells - Effects of IGF-I on Na+ uptake -)

  • 한호재;박권무;이장헌;양일석
    • 대한수의학회지
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    • 제36권4호
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    • pp.783-794
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    • 1996
  • 이온운반계는 생체의 각기 다른 세포의 성장을 조절하는 성장조절인자들의 효과를 매개하는데 깊은 관련이 있는 것으로 보고되고 있다. 신장 근위세뇨관에서 솔변 연 $Na^+/H^+$ 상호운반계는 사구체에서 여과된 나트륨의 재흡수와 수소이온의 분비를 조절하는 중요한 기능을 수행한다. 이 연구는 초대배양된 신장 근위세뇨관세포의 나트륨 운반을 Insulin-like Growth Factor-I(IGF-I)이 어떤 경로를 통하여 조절하는지를 알아보고자 실시하였다. 결과는 아래와 같다. 1. 초대배양된 신장 근위세뇨관세포에서 $Na^+$ uptake는 시간의존적으로 증가되었으며, 30분동안 $Na^+$ uptake를 실시한 결과 세포외 NaCl 농도의존적으로 $Na^+$ uptake를 유의성있게 감소시켰다(대조군; $40.11{\pm}1.76$, 140mM군; $17.82{\pm}0.94pmole\;Na^+/mg\;protein/min$). 2. $Na^+$ uptake는 iodoacetic acid(IAA, $1{\times}10^{-4}M$) 또는 valinomycin($5{\times}10^{-6}M$)처리시 대조군에 비해 각각 $50.51{\pm}4.4%$$57.65{\pm}2.27%$ 억제되었으며, ouabain($5{\times}10^{-5}M$)을 처리한 경우는 $140.23{\pm}3.37%$ 증가되었다. IGF-I($1{\times}10^{-5}M$)으로 배양한 세포를 actinomycin D($1{\times}10^{-7}M$)와 cycloheximide($4{\times}10^{-5}M$)로 처리시 $Na^+$ uptake는 대조군에 비해 각각 $90.21{\pm}2.39%$$89.64{\pm}3.69%$로 감소되었다. 3. IGF-I으로 배양한 세포에서 세포외 cAMP는 농도의존적($10^{-8}-10^{-4}M$)으로 $Na^+$ uptake를 유의성있게 감소시켰고, 3-isobutyl-1-methyl-xanthine(IBMX, $5{\times}10^{-5}M$)도 억제시켰다. Pertussis toxin(PTX, 50pg/ml)이나 cholera toxin(CTX, $1{\mu}g/ml$)의 처리시에도 $Na^+$ uptake는 억제되었다. 세포외 phorbol 12-myristate 13 acetate(PMA) 또한 농도의존적(1-100ng/ml)으로 $Na^+$ uptake를 감소시켰다. 그러나 staurosporine($1{\times}10^{-7}M$)은 $Na^+$ uptake에 영향을 미치지 않았으며 PMA와 stauiosporine을 동시에 처리했을 때도 $Na^+$ uptake는 억제되지 않았다. 결론적으로 초대배양된 토끼 신장 근위세뇨관세포에서 $Na^+$ uptake는 막전위와 세포내 에너지 의존적이며 IGF-I은 부분적으로 단백질 및 RNA 합성을 통해서 그리고 세포내 cAMP나 PKC 경로를 통해서 $Na^+$ uptake를 조절하는 것으로 생각된다.

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