• Title/Summary/Keyword: Mitochondrial ATP

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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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    • v.32 no.3
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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.

Identification of Novel SNPs with Effect on Economic Traits in Uncoupling Protein Gene of Korean Native Chicken

  • Oh, J.D.;Kong, H.S.;Lee, J.H.;Choi, I.S.;Lee, S.J.;Lee, S.G.;Sang, B.D.;Choi, C.H.;Cho, B.W.;Jeon, G.J.;Lee, H.K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.8
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    • pp.1065-1070
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    • 2006
  • The avian uncoupling protein (avUCP) is a member of the mitochondrial transporter superfamily that uncouples proton entry in the mitochondrial matrix from ATP synthesis. The sequencing analysis method was used to identify nucleotide polymorphisms within the avUCP gene in Korean native chicken (KNC). This study identified ten single nucleotide polymorphisms (SNPs) in the avUCP gene. We analyzed the SNPs of the avUCP gene to investigate whether polymorphism in the gene might be responsible for quantitative variations in economic traits in KNC. Three significant polymorphic sites for economic traits were avUCP C+282T (mean body weight, p<0.05), avUCP C+433T (daily percent lay, p<0.05), and avUCP T+1316C (daily percent lay, p<0.05). The frequency of each SNP was 0.125 (C+282T in avUCP gene exon 1 region), 0.150 (C+433T in avUCP gene intron 1 region), and 0.15 (T+1316C in avUCP gene exon 3 region), respectively. Among the identified SNPs, one pair of SNPs (genotype CC, C+282T and TT, avUCP C+433T) showed the highest daily percent lay (p<0.05) and mean body weight (p<0.05) and the frequency was 0.067. This study of the avUCP gene could be useful for genetic studies of this gene and selection on economic traits for KNC.

TOMM20 as a potential therapeutic target of colorectal cancer

  • Park, Sang-Hee;Lee, Ah-Reum;Choi, Keonwoo;Joung, Soyoung;Yoon, Jong-Bok;Kim, Sungjoo
    • BMB Reports
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    • v.52 no.12
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    • pp.712-717
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    • 2019
  • Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20's contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer.

Adverse Effect of Superovulation Treatment on Maturation, Function and Ultrastructural Integrity of Murine Oocytes

  • Lee, Myungook;Ahn, Jong Il;Lee, Ah Ran;Ko, Dong Woo;Yang, Woo Sub;Lee, Gene;Ahn, Ji Yeon;Lim, Jeong Mook
    • Molecules and Cells
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    • v.40 no.8
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    • pp.558-566
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    • 2017
  • Regular monitoring on experimental animal management found the fluctuation of ART outcome, which showed a necessity to explore whether superovulation treatment is responsible for such unexpected outcome. This study was subsequently conducted to examine whether superovulation treatment can preserve ultrastructural integrity and developmental competence of oocytes following oocyte activation and embryo culture. A randomized study using mouse model was designed and in vitro development (experiment 1), ultrastructural morphology (experiment 2) and functional integrity of the oocytes (experiment 3) retrieved after PMSG/hCG injection (superovulation group) or not (natural ovulation; control group) were evaluated. In experiment 1, more oocytes were retrieved following superovulation than following natural ovulation, but natural ovulation yielded higher (p < 0.0563) maturation rate than superovulation. The capacity of mature oocytes to form pronucleus and to develop into blastocysts in vitro was similar. In experiment 2, a notable (p < 0.0186) increase in mitochondrial deformity, characterized by the formation of vacuolated mitochondria, was detected in the superovulation group. Multivesicular body formation was also increased, whereas early endosome formation was significantly decreased. No obvious changes in other microorganelles, however, were detected, which included the formation and distribution of mitochondria, cortical granules, microvilli, and smooth and rough endoplasmic reticulum. In experiment 3, significant decreases in mitochondrial activity, ATP production and dextran uptake were detected in the superovulation group. In conclusion, superovulation treatment may change both maturational status and functional and ultrastuctural integrity of oocytes. Superovulation effect on preimplantation development can be discussed.

Mitochondrial Genome of Spirometra theileri Compared with Other Spirometra Species

  • Ndosi, Barakaeli Abdieli;Park, Hansol;Lee, Dongmin;Choe, Seongjun;Kang, Yeseul;Nath, Tilak Chandra;Bia, Mohammed Mebarek;Eamudomkarn, Chatanun;Jeon, Hyeong-Kyu;Eom, Keeseon S.
    • Parasites, Hosts and Diseases
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    • v.59 no.2
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    • pp.139-148
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    • 2021
  • This study was carried out to provide information on the taxonomic classification and analysis of mitochondrial genomes of Spirometra theileri. One strobila of S. theileri was collected from the intestine of an African leopard (Panthera pardus) in the Maswa Game Reserve, Tanzania. The complete mtDNA sequence of S. theileri was 13,685 bp encoding 36 genes including 12 protein genes, 22 tRNAs and 2 rRNAs with absence of atp8. Divergences of 12 protein-coding genes were as follow: 14.9% between S. theileri and S. erinaceieuropaei, 14.7% between S. theileri and S. decipiens, and 14.5% between S. theileri with S. ranarum. Divergences of 12 proteins of S. theileri and S. erinaceieuropaei ranged from 2.3% in cox1 to 15.7% in nad5, while S. theileri varied from S. decipiens and S. ranarum by 1.3% in cox1 to 15.7% in nad3. Phylogenetic relationship of S. theileri with eucestodes inferred using the maximum likelihood and Bayesian inferences exhibited identical tree topologies. A clade composed of S. decipiens and S. ranarum formed a sister species to S. erinaceieuropaei, and S. theileri formed a sister species to all species in this clade. Within the diphyllobothridean clade, Dibothriocephalus, Diphyllobothrium and Spirometra formed a monophyletic group, and sister genera were well supported.

Species diversity and distribution of the genus Colpomenia (Scytosiphonaceae, Phaeophyceae) along the coast of China

  • Song, Xiao-Han;Hu, Zi-Min;Sun, Zhong-Min;Draisma, Stefano G.A.;Fresia, Pablo;Duan, De-Lin
    • ALGAE
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    • v.34 no.3
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    • pp.217-228
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    • 2019
  • The marine brown algal genus Colpomenia has a worldwide distribution, with five species reported in Korea and Japan. However, no studies to date attempted to identify the number of species and geographical distribution of Colpomenia along Chinese coast. To fill the biodiversity knowledge gap, we analyzed 63 mitochondrial cox3 and 62 mitochondrial atp6 sequences of Colpomenia specimens collected from 30 localities along the Chinese coast. Maximum likelihood and Bayesian inference trees suggest the presence of at least three Colpomenia species (i.e., C. peregrina, C. claytoniae, and C. sinuosa) in China. C. peregrina and C. claytoniae are documented for the first time. C. sinuosa was only found in the South China Sea and its distribution didn't overlap with that of C. peregrina which was found in the Yellow-Bohai Sea and the East China Sea. C. claytoniae appears to be confined to three isolated islands in the East and the South China Sea, where it occurs in sympatry with, respectively, C. peregrina and C. sinuosa. Future study can focus on comparing eco-physiological differences of Colpomenia species in response to environmental variables and exploring possible genetic hybridization / introgression at inter-specific contact zones.

Protective Effect of Phragmitis Rhizoma against Oxidative Stress-induced DNA Damage and Apoptosis in Chang Liver Cells (산화적 스트레스에 의한 간세포의 DNA 손상 및 apoptosis 유도에 대한 노근 추출물의 보호 효과)

  • Lee, Hui yeong;Hong, Sang hoon;Park, Sang eun
    • The Journal of Internal Korean Medicine
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    • v.42 no.6
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    • pp.1269-1284
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    • 2021
  • Objectives: Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis Trin., which has been prescribed in traditional Korean medicine to relieve fever and vomiting and to nourish the body fluids. Recently, the protective effect of Phragmitis Rhizoma extract or its components on myelotoxicity and inflammatory responses have been reported, but no study has yet been conducted on oxidative stress. Methods: The present study investigated whether an ethanol extract of Phragmitis Rhizoma (PR) could protect against cellular damage induced by oxidative stress in Chang liver cells. Results: Pretreatment with PR significantly suppressed the hydrogen peroxide (H2O2)-induced reduction of Chang cell viability and generation of reactive oxygen species (ROS), thereby deferring apoptosis. PR also markedly inhibited H2O2-induced comet tail formation and phospho-γH2AX expression, suggesting that PR protected against oxidative stress-mediated DNA damage. PR also effectively prevented the inhibition of ATP synthesis in H2O2-treated Chang cells by inhibiting the loss of mitochondrial membrane potential, indicating that PR maintains energy metabolism through preservation of mitochondrial function while eliminating ROS generated by H2O2. Immunoblotting results indicated that PR attenuated the H2O2-induced downregulation of Bcl-2 and upregulation of Bax expression. Conclusions: PR protects against oxidative injury in Chang liver cells by regulating energy homeostasis via ROS generation blockade, which is at least partly mediated through inactivation of the mitochondria-mediated apoptosis pathway.

The Formation and Change of Cytochrome-c-oxidase in the Mitochondria of the Bovine Cardiac Muscle (우(牛)심근조직의 mitochondria에서 cytochrome-c-oxidase의 형성과 변화)

  • Kim, Soo-Jin
    • Applied Microscopy
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    • v.38 no.2
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    • pp.125-133
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    • 2008
  • Cytochrome-c-oxidase in mitochondria membrane is one of the most important factors for energy generation in the cell. As well as it is electron transfer enzyme, it is also heavily related to the apoptosis and other pathologic conditions. Meanwhile, porin is a protein located in inner and outer membranes of mitochondria, which is assumed to be functionally correlated with cytochrome-c-oxidase. It functions as forming electron transfer chain and conveying ATP. Therefore, using the immune-microscopy, It compared the distribution of cytochrome-c-oxidase and porin to figure out the formation and changes on cytochrome-c-oxidase in mitochondrial cristae. The sarcroplasm of cardic muscle tissue has many mitochondria. They are classified into two groups: the mitochondria with many cytochrome-c-oxidase and the mitochondria with only porins. The mitochondria with porins had few cytochrome-c-oxidases in their membrane; in contrast, the other mitochondria with rich cytochrome-c-oxidase had few porins in their walls. In addition, according to the location of the tissue in bovine heart, distribution of those kind of mitochondria had been clearly separated. As a result, it could be assumed that immature mitochondria has many porins to transfer the protein materials from sarcroplasm through the porins, and they made cytochrome-c-oxidase until it is enough, and then they decreased the porin and maintained minimum number of the porin.

Regulation of NAD+- Specific Isocitrate Dehydrogenase from Pythium ultimum

  • Kim, Hak-Ryul;Weete, John D.
    • BMB Reports
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    • v.32 no.4
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    • pp.385-392
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    • 1999
  • The $NAD^+$-specific activity of a dual coenzyme-specific isocitrate dehydrogenase (IDH; EC 1.1.1.41) from the primitive fungus Pythium ultimum was investigated to elucidate the regulatory factors that may influence the intracellular distribution of carbon and the availability of intermediates, e.g. citrate, for fatty acid synthesis. Inhibition of $NAD^+$-IDH activity by diphospho- and triphosphonucleotides (ATP, ADP, and GTP) reflected the sensitivity of this enzyme to cellular energy charge even though monophosphonucleotides (AMP and GMP) had little effect on activity. NADPH, but not NADH, substantially inhibited $NAD^+$-IDH activity, showing noncompetitive inhibition with isocitrate. Oxalacetate and ${\alpha}$-ketoglutarate showed competitive inhibition with isocitrate, while citrate and cis-aconitate showed mixed-noncompetitive inhibition with isocitrate. Inhibition by these substances ranged from 29 to 46% at 10 mM. The inhibitory effect of oxalacetate was increased synergistically by glyoxylate, which alone caused 31% uncompetitive inhibition at 10 mM, and a mixture of the two substances at 1 mM each showed 98% inhibition of $NAD^+$-IDH activity. The regulation of $NAD^+$-IDH in Pythium ultimum seems to be a complex process involving mitochondrial metabolites. The addition of glyoxylate (3 mM) and oxalacetate (3 mM) to the culture medium resulted in the production of 49% more lipid by P. ultimum.

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May Low Level Laser Therapy be the Candidate of First Choice for the Acute Stroke? (중풍 급성기에 있어서 레이저치료에 대한 최신지견 고찰 : 임상 논문을 중심으로)

  • Yang, Chang-Sop;Jang, In-Soo;Sun, Seung-Ho
    • The Journal of Internal Korean Medicine
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    • v.31 no.3
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    • pp.612-619
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    • 2010
  • Background : Low level laser therapy may be an effective method to protect tissue damage in acute stroke. Recently, series of clinical studies on the basis of animal experiments report efficacy and safety of laser therapy at early stages of acute stroke. Laser promotes mitochondrial ATP synthesis to reduce cell death by ischemic infarction. Objectives : To report possibility of non-invasive laser therapy for acute stroke by reviewing literature about its effectiveness, safety and mechanism. Methods : We searched papers using PubMed and 'Web of Knowledge' of Thomson ISI, using the keywords "Laser Therapy, Low-Level" and "Stroke". Limitations were last 10 years of publications and only in English. Search range includes RCTs, clinical reports, reviews and animal experiments. Papers not matched with inclusion criteria were excluded. Results : A total 223 studies were found, 203 excluded during title and extract screening. After scanning 20 papers the final 2 serial RCTs were selected and analyzed. They reported that transcranial laser therapy led in neuroprotective effect for acute stroke patents. Clinical evaluation factors showed favorable trend and initial safety. Conclusions : Non-invasive laser secured safety of clinical application. It may be a favorable choice for the acute stage of stroke.