• 제목/요약/키워드: Warburg effects

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Targeting Cancer Metabolism - Revisiting the Warburg Effects

  • Tran, Quangdon;Lee, Hyunji;Park, Jisoo;Kim, Seon-Hwan;Park, Jongsun
    • Toxicological Research
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    • 제32권3호
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    • pp.177-193
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    • 2016
  • After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism.

Corrosion Properties of Dissimilar Friction Stir Welded 6061 Aluminum and HT590 Steel

  • Seo, Bosung;Song, Kuk Hyun;Park, Kwangsuk
    • Metals and materials international
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    • 제24권6호
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    • pp.1232-1240
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    • 2018
  • Corrosion properties of dissimilar friction stir welded 6061 aluminum and HT590 steel were investigated to understand effects of galvanic corrosion. As cathode when coupled, HT590 was cathodically protected. However, the passivation of AA6061 made the aluminum alloy cathode temporarily, which leaded to corrosion of HT590. From the EIS analysis showing Warburg diffusion plot in Nyquist plots, it can be inferred that the stable passivation layer was formed on AA6061. However, the weld as well as HT590 did not show Warburg diffusion plot in Nyquist plots, suggesting that there was no barrier for corrosion or even if it exists, the barrier had no function for preventing and/or retarding charge transport through the passivation layer. The open circuit potential measurements showed that the potential of the weld was similar to that of HT590, which lied in the pitting region for AA6061, making the aluminum alloy part of the weld keep corrosion state. That resulted in the cracked oxide film on AA6061 of the weld, which could not play a role of corrosion barrier.

Protein phosphatase 4 dephosphorylates phosphofructokinase-1 to regulate its enzymatic activity

  • Jaehong Park;Dong-Hyun Lee
    • BMB Reports
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    • 제56권11호
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    • pp.618-623
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    • 2023
  • Most cancer cells utilize glucose at a high rate to produce energy and precursors for the biosynthesis of macromolecules such as lipids, proteins, and nucleic acids. This phenomenon is called the Warburg effect or aerobic glycolysis- this distinct characteristic is an attractive target for developing anticancer drugs. Here, we found that Phosphofructokinase-1 (PFK-1) is a substrate of the Protein Phosphatase 4 catalytic subunit (PP4C)/PP4 regulatory subunit 1 (PP4R1) complex by using immunoprecipitation and in vitro assay. While manipulation of PP4C/PP4R1 does not have a critical impact on PFK-1 expression, the absence of the PP4C/PP4R1 complex increases PFK-1 activity. Although PP4C depletion or overexpression does not cause a dramatic change in the overall glycolytic rate, PP4R1 depletion induces a considerable increase in both basal and compensatory glycolytic rates, as well as the oxygen consumption rate, indicating oxidative phosphorylation. Collectively, the PP4C/PP4R1 complex regulates PFK-1 activity by reversing its phosphorylation and is a promising candidate for treating glycolytic disorders and cancers. Targeting PP4R1 could be a more efficient and safer strategy to avoid pleiotropic effects than targeting PP4C directly.

제4급 인산염을 이용한 과염소산 이온선택성 PVC막 전극의 전극전위와 AC 임피던스 특성 (Characteristics of Electrode Potential and AC Impendance of Perchlorate Ion-Selective Electrodes Based on Quaternary Phosphonium Salts in PVC Membranes)

  • 안형환
    • 멤브레인
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    • 제9권4호
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    • pp.230-239
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    • 1999
  • 운반체(감응물질)로 제 4급 인산염을 사용하여 PVC를 지지체로 하여 과염소산이온의 농도 $10^{-6}$ M까지 선형적인 이온선택성 전극을 제작하였다. 운반체의 화학적구조와 함량 가소제의 종류 및 막 두께에 따른 전극의 기울기 선형응답범위 및 한계측정농도 등 전극전위특성을 고려하여 최적의 과염소산 이온선택성 PVC막 전극을 제조한 다음 측정 가능한 pH 범위 선택계수 및 전극의 교류임피던스 특성을 비교 검토하였다 운반체로 tetraoctyl-phosphonium perchlorate(TOPP) tetraphenylphosphonium perchlorate(TPPP) 및 tetrabutylphosponium perchlorate (TBPP)_ 등의 제 4급 인산염의 과염소산 이온 치환체를 사용하였다 알킬기의 탄소고리 수가 증가할수록 전극특성은 TBPP$^P{ClO}_4$, 선형응답범위 $10^{-1}$\times$10^{-6}$ M 및 한계측정농도는 9.66$\times$$10^{-7}$ M 이었으며 시판되고 있는 Orion 전극특성보다 좋은 결과를 나타내었다 전극전위는 pH3~11범위에서 ph의 영향을 받지 않았으며 ${CIO}_4$ 에 대한 방해이온의 선택계수 서열은 ${SO}^2_4$ < F < Br < I 이었다 임피던스 측정결과 TOPP의 경우 등가회로는 용액저항 이중층용량과 벌크저항의 병렬 및 Warburg 임피던스의 직렬이었다 이 경우 용액저항은 거의 나타나지 않았고 확산에 의한 Warburg 임피던스는 크게 나타났으며 Warburg 계수는 1.32$\times$$10^74 $\Omega$ $\cdot$ ${cm}^2/s^{1/2}$이었다.

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Chlorella의 생리에 미치는 Indole acetic acid의 영향 (Physiological effects of indole acetic acid (IAA) on chlorella ellipsoidea)

  • 채인기
    • 미생물학회지
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    • 제10권3호
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    • pp.117-127
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    • 1972
  • To study the effect of IAA on the growth of Chlorella, the alage wre cultured on the media for six days by bubbling $_{2}$ enriched air under 10K lux at 20-$25^{\circ}C$. The culture media were made by adding a concentration of $10^{-3}$M, $10^{-4}$M, and 0M(as a control) IAA to the standard media. During the period of culture, Chlorella was smapled for the given time of interval and photosynthetic and respiratory activities were measured by Warburg manometer and change of chemical components of Chlorella was determined by spectrophotometry after the Chlorella cell was fractionated by Schmidt-Thannhauser method. 1) Photosynthetic and respiratory activities were enhanced by IAA ; especially the enhancement of respiratory activity was so remarkable. 2) As to the chemical components of Chlorella, carbohydrates and amino acids were reduced a little but phosphate, RNA, DNA, and protein were increased by $10^{-3}$M IAA ; the increase of RNA, in particular, was noticable. 3) The above results suggest that the enhancement of growth of Chlorella, by IAA and ATP induced by respiratory activity accelerated with IAA enhanced RNA synthesis, resulting in an increase of protein synthesis.

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탄수화물과 황산암모늄이 Pseudomonas diminuta의 리그닌 분해에 미치는 영향 (Effects of Some Carbohydrates and Ammonium Sulfate on Lignin Degradation by Pseudomonas diminuta)

  • 김규중;신광수;맹진수;성치남
    • 미생물학회지
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    • 제26권2호
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    • pp.129-136
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    • 1988
  • To investigate the influence of cosubstrate supplement and ammonium sulfate on lignin degradation by Pseudomonas diminuta KM-4-2, isolated in the laboratory, the strain was cultured on the lignin media which contained lignin as a source of carbon and the culture filtrate was analyzed by Sephadex G-75 column chromatography. It was found that polymerization was not appeared unlike wood-rot fungi. When the carbohydrates were added, the peak of lignin at 280nm by UV scanning spectra of the filtrate, was significantly increased. In order to determine the effect of ammonium sulfate on the ligninolytic activity, the isolated strain was incubated in the media containing 0.1%, 0.25% and 0.5% of nitrogen concentration in the Warburg flask and the rate of oxygen uptake was esitmated by Warbuge Respirometer. As a result, the activity was maximum at 0.1% of nitrogen concentration and thereafter decreased in parallel with nitrogen concentration.

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Lactate: a multifunctional signaling molecule

  • Lee, Tae-Yoon
    • Journal of Yeungnam Medical Science
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    • 제38권3호
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    • pp.183-193
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    • 2021
  • Since its discovery in 1780, lactate has long been misunderstood as a waste by-product of anaerobic glycolysis with multiple deleterious effects. Owing to the lactate shuttle concept introduced in the early 1980s, a paradigm shift began to occur. Increasing evidence indicates that lactate is a coordinator of whole-body metabolism. Lactate is not only a readily accessible fuel that is shuttled throughout the body but also a metabolic buffer that bridges glycolysis and oxidative phosphorylation between cells and intracellular compartments. Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells and tissues, resulting in diverse biological consequences including decreased lipolysis, immune regulation, anti-inflammation, wound healing, and enhanced exercise performance in association with the gut microbiome. Furthermore, lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones, accounting for its key role in immune modulation and maintenance of homeostasis.

Pseudomonas fluorescens에 대한 furfural의 독성효과에 관하여 (Toxic effects of furfural on Pseudomonas fluorescens)

  • 김태용;하영칠;홍순우
    • 미생물학회지
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    • 제21권3호
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    • pp.149-155
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    • 1983
  • Furfural을 유일한 탄소원으로 이용하지 뭇하는 것으로 알려졌던 Pseudomonas jlµorescens가 호조건하에서 저농도의 furfural은 이용가능함을 밝혔다. 이 균주가 고농도의 furfural은 잘 이용하지 못하는 것은 furfural이 균주에 대해 다음과 같은 독성효과를 나타내기 때문이다. 1. 0.01% 정도의 furfural에 의해서 잠재기가 연장되었고 특히 생장초기의 균체에 더 큰 억제효과가 나타나 잠재기의 연장과 동시에 균체수율도 감소하였다. 2. 0.1% 이상의 furfural은 치사효과를 나타냈으며 대사활성도가 클수록 치사율이 높았고 치사율에 차이가 나타나 생장초기의 균체가 더 큰 치사율을 나타냈다. 3. Furfural이 호흡률에 대해서는 별다른 영향을 나타내지 않았다.

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Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents

  • Lee, Sujin;Kang, Sunmi;Park, Sunghyouk
    • 한국자기공명학회논문지
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    • 제21권1호
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    • pp.31-43
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    • 2017
  • Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

급성 신장 빈혈이 신장의 유기성 대사에 미치는 영향 (Effects of Acute Renal Ischemia on Aerobic Metabolism of Rabbit Kidney Homogenates)

  • 강석원
    • The Korean Journal of Physiology
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    • 제6권2호
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    • pp.9-17
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    • 1972
  • This experiment was carried out to investigate systematically how the aerobic metabolic capacity of renal tissue reduced by the effects of a period of induced ischemia. Aerobic metabolic studies were performed on homogenates of cortex and medulla of rabbits. Ischemia was induced by occluding the renal vein or renal artery of the left kidney for an hour. The right kidney used as a paired control. Aerobic metabolism was asesssed by measuring the oxygen consumption using the Warburg's manometric apparatus. The results are summarized as follows: 1. One hour of occlusive ischemia does not increase in the kidney weight in the renal arterial occlusion but increase in the renal venous occlusion. 2. Occlusion of either the renal vein or renal artery for an hour did not reduce to any significant degree the level of endogenous substrate in cortical homogenates as measured the rates of $0_2$ consumption. 3. A significant reduction in the rate of $C_2$ consumption was noted in the medullary homogenates of renal venous occluded kidneys while renal arterial occlusion had less of an effect. 4. The capaciy of homogenates for aerobic metabolism is not reduced by acute ischemia, because of the higher rate of oxygen consumption induced by exogenous glucose in renal vein occlusion. 5. The oxygen consumption of medullary homogenate more decreased to acute ischemia than cortical homogenates. The results of this investigation suggest that one hour circulatory stasis does not reduce major potential capacity of renal cortical tissue at the subcellular level to produce energy. In contrast, the aerobic metabolism of medullary tissue is reduced by renal ischemia. Further, both cortex and medulla appear to be more sensitive to ischemia induced by renal venous occlusion than by renal arterial occlusion.

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