• Title/Summary/Keyword: glycolysis

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Cancer stem cell metabolism: target for cancer therapy

  • Chae, Young Chan;Kim, Jae Ho
    • BMB Reports
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    • v.51 no.7
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    • pp.319-326
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    • 2018
  • Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differentiated bulk tumor cells, and these specific metabolic activities directly participate in the process of CSC transformation or support the biological processes that enable tumor progression. Exploring the role of CSC metabolism and the mechanism of the metabolic plasticity of CSCs has become a major focus in current cancer research. The targeting of CSC metabolism may provide new effective therapies to reduce the risk of recurrence and metastasis. In this review, we summarize the most significant discoveries regarding the metabolism of CSCs and highlight recent approaches in targeting CSC metabolism.

Deregulation of Aspartokinase by Single Nucleotide Exchange Leads to Global Flux Rearrangement in the Central Metabolism of Corynebacterium glutamicum

  • Kim Hyung-Min;Heinzle Elmar;Wittmann Christoph
    • Journal of Microbiology and Biotechnology
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    • v.16 no.8
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    • pp.1174-1179
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    • 2006
  • The wild-type Corynebacterium glutamicum ATIC 13032 and Corynebacterium glutamicum ATTC 13032 lysC S301Y, exhibiting a deregulated aspartokinase, were compared concerning growth, lysine production, and intracellular carbon fluxes. Both strains differ by only one single nucleotide over the whole genome. In comparison to the wild-type, the mutant showed significant production of lysine with a molar yield of 0.087 mol (mol glucose$^{-1}$) whereas the biomass yield was reduced. The deregulation of aspartokinase further led to a global rearrangement of carbon flux throughout the whole central metabolism. This involved an increased flux through the pentose phosphate pathway (PPP) and an increased flux through anaplerosis. Because of this, the mutant revealed an enhanced supply of NADPH and oxaloacetate required for lysine biosynthesis. Additionally, the lumped flux through phosphoenolpyruvate carboxykinase and malic enzyme, withdrawing oxaloacetate back to the glycolysis and therefore detrimental for lysine production, was increased. The reason for this might be a contribution of malic enzyme to NADPH supply in the mutant in the mutant. The observed complex changes are remarkable, because they are due to the minimum genetic modification possible, the exchange of only one single nucleotide.

Transcriptional Profiling of the Trichoderma reesei Recombinant Strain HJ48 by RNA-Seq

  • Huang, Jun;Wu, Renzhi;Chen, Dong;Wang, Qingyan;Huang, Ribo
    • Journal of Microbiology and Biotechnology
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    • v.26 no.7
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    • pp.1242-1251
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    • 2016
  • The ethanol production of Trichoderma reesei was improved by genome shuffling in our previous work. Using RNA-Seq, the transcriptomes of T. reesei wild-type CICC40360 and recombinant strain HJ48 were compared under fermentation conditions. Based on this analysis, we defined a set of T. reesei genes involved in ethanol production. Further expression analysis identified a series of glycolysis enzymes, which are upregulated in the recombinant strain HJ48 under fermentation conditions. The differentially expressed genes were further validated by qPCR. The present study will be helpful for future studies on ethanol fermentation as well as the roles of the involved genes. This research reveals several major differences in metabolic pathways between recombinant strain HJ48 and wild-type CICC40360, which relates to the higher ethanol production on the former, and their further research could promote the development of techniques for increasing ethanol production.

Epinephrine-induced lactic acidosis in orthognathic surgery: a report of two cases

  • Son, Hee-Won;Park, Se-Hun;Cho, Hyun-Oh;Shin, Yong-Joon;Son, Jang-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.42 no.5
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    • pp.295-300
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    • 2016
  • Submucosal infiltration and the topical application of epinephrine as a vasoconstrictor produce excellent hemostasis during surgery. The hemodynamic effects of epinephrine have been documented in numerous studies. However, its metabolic effects (especially during surgery) have been seldom recognized clinically. We report two cases of significant metabolic effects (including lactic acidosis and hyperglycemia) as well as hemodynamic effects in healthy patients undergoing orthognathic surgery with general anesthesia. Epinephrine can induce glycolysis and pyruvate generation, which result in lactic acidosis, via ${\beta}2$-adrenergic receptors. Therefore, careful perioperative observation for changes in plasma lactate and glucose levels along with intensive monitoring of vital signs should be carried out when epinephrine is excessively used as a vasoconstrictor during surgery.

Proteomic Changes in the Sound Vibration-Treated Arabidopsis thaliana Facilitates Defense Response during Botrytis cinerea Infection

  • Ghosh, Ritesh;Choi, Bosung;Kwon, Young Sang;Bashir, Tufail;Bae, Dong-Won;Bae, Hanhong
    • The Plant Pathology Journal
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    • v.35 no.6
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    • pp.609-622
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    • 2019
  • Sound vibration (SV) treatment can trigger various molecular and physiological changes in plants. Previously, we showed that pre-exposure of Arabidopsis plants to SV boosts its defense response against Botrytis cinerea fungus. The present study was aimed to investigate the changes in the proteome states in the SV-treated Arabidopsis during disease progression. Proteomics analysis identified several upregulated proteins in the SV-infected plants (i.e., SV-treated plants carrying Botrytis infection). These upregulated proteins are involved in a plethora of biological functions, e.g., primary metabolism (i.e., glycolysis, tricarboxylic acid cycle, ATP synthesis, cysteine metabolism, and photosynthesis), redox homeostasis, and defense response. Additionally, our enzyme assays confirmed the enhanced activity of antioxidant enzymes in the SV-infected plants compared to control plants. Broadly, our results suggest that SV pre-treatment evokes a more efficient defense response in the SV-infected plants by modulating the primary metabolism and reactive oxygen species scavenging activity.

Convergence of Cancer Metabolism and Immunity: an Overview

  • Van Dang, Chi;Kim, Jung-whan
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.4-9
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    • 2018
  • Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Tetrahydropteridines possess antioxidant roles to guard against glucose-induced oxidative stress in Dictyostelium discoideum

  • Park, Seon-Ok;Kim, Hye-Lim;Lee, Soo-Woong;Park, Young Shik
    • BMB Reports
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    • v.46 no.2
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    • pp.86-91
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    • 2013
  • Glucose effects on the vegetative growth of Dictyostelium discoideum Ax2 were studied by examining oxidative stress and tetrahydropteridine synthesis in cells cultured with different concentrations (0.5X, 7.7 g $L^{-1}$; 1X, 15.4 g $L^{-1}$; 2X, 30.8 g $L^{-1}$) of glucose. The growth rate was optimal in 1X cells (cells grown in 1X glucose) but was impaired drastically in 2X cells, below the level of 0.5X cells. There were glucose-dependent increases in reactive oxygen species (ROS) levels and mitochondrial dysfunction in parallel with the mRNA copy numbers of the enzymes catalyzing tetrahydropteridine synthesis and regeneration. On the other hand, both the specific activities of the enzymes and tetrahydropteridine levels in 2X cells were lower than those in 1X cells, but were higher than those in 0.5X cells. Given the antioxidant function of tetrahydropteridines and both the beneficial and harmful effects of ROS, the results suggest glucose-induced oxidative stress in Dictyostelium, a process that might originate from aerobic glycolysis, as well as a protective role of tetrahydropteridines against this stress.

Isolation and Characterization of the Streptococcus mutans from Korean Children with Caries

  • Kang, Kyung-Hee;Kim, Ji-Young;Nam, Jin-Sik;Jin, Ingn-Yol
    • Biomedical Science Letters
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    • v.13 no.4
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    • pp.341-347
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    • 2007
  • Streptococcus mutans, one of a major causal agents of dental caries, is component of the dental plaque and produces various organic acids such as lactic acid as the end-product of glycolysis. In this study, we isolated S. mutans from Korean children with caries and also investigated the expression of protein under acid stress. S. mutans was identified at the species level using a 16S ribosomal DNA sequencing comparison method. The primer specificity was tested on eleven S. mutans strains isolated from Korean children with caries. The data showed that eleven strains are S. mutans. At treatment of concentration of 20 mM lactic acid in the mid-log phage, K-7 exhibited the highest maximum culture OD compared with those of other groups. As a consequence, we examined the expression of protein under 20 mM lactic acid stress using S. mutans K-7. The results of 2D gel electrophoresis by image analysis showed that thirteen proteins are up-regulated under the stress. Further study is being focused on amino acid analysis by mass spectrometry in order to analyze those spots.

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F-18 FDG Uptake in a Toxic Autonomous Thyroid Nodule

  • Lee, Myoung-Hoon;Park, Chan-H.;Kim, Hyun-Soo;Yoon, Seok-Nam;Hwang, Kyung-Hoon
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.4
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    • pp.286-287
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    • 2001
  • A 44 year-old male patient was undergoing diagnosis and therapy for acute myelogenous leukemia (AML, M2). On physical examination a thyroid mass was palpated in the left lower lobe. He had palpitation and intolerance to heat. Thyroid function tests revealed hyperthyroidism; T3: 150ng/dl (N:60-90), fT4: 2.26 ng/dl (N:0.70-1.80), TSH: 0.01 ulU/ml (N:0.25-5.00). Ultrasonography demonstrated a hypoechoic mass with scattered calcifications measuring 2.55 2.03 3.64 cm in size. F-18 FDG camera-based PET scan performed as a follow-up study of AML revealed a focal increased uptake in the left neck, where an autonomous nodule was detected on Tc-99m thyroid scan. After the diagnosis of toxic autonomous nodule, Goetz disease, he underwent surgical nodulectomy. Microscopically, the nodule contained follicular proliferation with degenerative change but without evidence of thyroid carcinoma. Focal uptake in autonomous thyroid nodules is due to increased glycolysis within the nodules.

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식육의 연화증진에 관한 최근의 연구동향 - 적색육의 연도 증진에 이용되는 전기자극의 작용 -

  • 황인호
    • Proceedings of the Korean Society for Food Science of Animal Resources Conference
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    • 2002.05a
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    • pp.17-25
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    • 2002
  • Application of electrical stimulation in the red meat species (eg. beef and sheep) processing has been erratic around the world and this may reflect an incomplete knowledge of how to optimise the technology. Although it is well established that stimulation increases the rate of post-mortem glycolysis other biochemical and biophysical effects have been implicated with the use of this technology. On the basis of currently available knowledge, this mini-review seeks to examine the current theories about the effect of stimulation on post-mortem muscle. The classical view that stimulation prevents muscle from shortening excessively during rigor development has been expanded to include the possibility that it also results in physical disruption of muscle structure. The interaction of these effects with the acceleration of the rate of proteolysis through activation of the calpain protease system has not been comprehensively reviewed in the past. As a result of conclusion driven, this article highlights several areas that may prove fruitful for further research. The challenge for further development of electrical stimulation systems is optimisation of the activation of the enzyme systems in parallel with manipulation of chilling regimes so as to ensure rigor mortis is achieved at temperatures which minimise shortening. The potential of regional stimulation of sections of the carcass to achieve this outcome is worthy of study given the different fibre composition of muscles and temperature gradients.

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