• Title/Summary/Keyword: Metabolic regulators

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Jinan red ginseng extract inhibits triglyceride synthesis via the regulation of LXR-SCD expression in hepatoma cells

  • Hwang, Seung-mi;Park, Chung-berm
    • Korean Journal of Food Science and Technology
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    • v.51 no.6
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    • pp.558-564
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    • 2019
  • Hypertriglyceridemia is one of the metabolic syndrome that is often observed as a result of lipid abnormalities. It is associated with other lipids, metabolic disorders, cardiovascular disease and liver disease. Korean red ginseng is known to affect obesity, dyslipidemia, liver disease and liver function, but the mechanism of its effect is not clear. This study examined the beneficial effects of hypertriglyceridemia and the mechanism of action of Jinan red ginseng extract (JRG) in hepatoma cells. To measure the levels of triglyceride accumulation, we studied the expression of proteins and mRNAs related to lipidogenesis in hepatoma cells (Huh7 and HepG2). JRG decreases the lipidogenic markers, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding proteins α (C/EBPα) and C/EBPβ which are major regulators of triglyceride synthesis in hepatoma cells. We also found that JRG reduced sterol regulatory element binding proteins 1c (SREBP-1c), C/EBPα and C/EBPβ by regulating liver X receptor (LXR) and stearoyl CoA desaturase (SCD) expressions. In addition, the first-limited step of synthesis triglyceride (TG), glycerol-3-phosphate (G3P) is decreased by JRG. These results suggest that the anti-hypertriglyceride effect of JRG in hepatoma cells could be accompanied with the inhibition of lipidogenic transcription factors by regulating LXR and SCD expression.

Expression of caveolin-3 as positive intracellular signaling regulator on the development of hypertrophy in cardiac tissues

  • Kim, Joo-Heon;Han, Jin;Kim, Yong-Kwon;Yang, Young-Ae;Hong, Yonggeun
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.537-544
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    • 2005
  • We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.

Melatonin Protects Chronic Kidney Disease Mesenchymal Stem/Stromal Cells against Accumulation of Methylglyoxal via Modulation of Hexokinase-2 Expression

  • Go, Gyeongyun;Yoon, Yeo Min;Yoon, Sungtae;Lee, Gaeun;Lim, Ji Ho;Han, Su-Yeon;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.28-37
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    • 2022
  • Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

Physiological Activities Exerted by Various Growth Regulators, Ca and K ion on Elongation of Soybean Hypocotyl Segments (대두유축신장에 미치는 각종생장 조절물질과 석탄 및 가리의 생리적작용에 대하여)

  • 곽병화
    • Journal of Plant Biology
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    • v.11 no.1
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    • pp.22-26
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    • 1968
  • Hypocotyl segments of shade-grown soybean sprouts(var. Kumdo) were floated in solutions of various substances at physiological levels and grown for either 24 hours at 28$^{\circ}C$ or 72 hours at $25^{\circ}C$. Increased length of the segments beyond 20mm (the original length) was obtained as a measure of the present studies. At the room temperature, Ca and DNP strongly inhibited elongation of the hypocotyl segments, whereas K, IAA, GA and EDTA in general promoted it. There were, however, no such differences in the effects at relatiely low temperature. This indicated that the elongation process not only involves stretching of wall materials, but also does synthesis of the materials. Ca was found to be antagonistic to the promotive action of GA in the elongation, and the IAA action involves metabolic energy. EDTA seemed to act as a widely known chelator removing Ca already existed in the hypocotyl tissue, thus shwoed a promotion in the elongation.

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A Review on Metabolism and Cancer in Relation with Circadian Clock Connection

  • Merlin Jayalal, L.P.
    • Journal of Integrative Natural Science
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    • v.5 no.3
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    • pp.198-210
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    • 2012
  • Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of the cell cycle, and alterations in clock function could lead to aberrant cellular proliferation. In addition, connections between the circadian clock and cellular metabolism have been identified that are regulated by chromatin remodelling. This suggests that abnormal metabolism in cancer could also be a consequence of a disrupted circadian clock. Therefore, a comprehensive understanding of the molecular links that connect the circadian clock to the cell cycle and metabolism could provide therapeutic benefit against certain human neoplasias.

Transcriptome Analysis Unveils Gln3 Role in Amino Acids Assimilation and Fluconazole Resistance in Candida glabrata

  • Santos, Francisco J. Perez-de los;Garcia-Ortega, Luis Fernando;Robledo-Marquez, Karina;Guzman-Moreno, Jesus;Riego-Ruiz, Lina
    • Journal of Microbiology and Biotechnology
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    • v.31 no.5
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    • pp.659-666
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    • 2021
  • After Candida albicans, Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata, Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

Effect of Plant Growth Regulator Treatment on Isoflavones in Soybean

  • Jinhee Seo;Seoyeon Hong;Hyerang Park;Jaesung Park;Okjae Won;Eunji Seo;Wonyoung Han;Kido Park
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.164-164
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    • 2022
  • The soybean (Glycine max(L.) Merrill), an important food crop in the world, is popular because of its high quality protein and oil content. Soybeans as a food have long been known for their beneficial effects on health and are well-recognized globally. Isoflavones, significant soybean secondary metabolic products, may be crucial in avoiding some cancers and lowering the risk of cardiovascular disorders. This study investigates the correlation between plant growth regulator and the effect on the isoflavone levels in soybean leaves. The study was carried out in the green-house of the southern crop department in miryang. Soybeans(Seonpung) were cultivated in 1/2000 of the Wagner pot. Ethephon(500, 1000, 2000 ppm) and ABA(100, 200, 400 ppm) were used as plant growth regulators, and they were each treated on R2, R5, and R7 stage. After treatment, leaves were sampled three times at intervals of 5 days, and the content of 6 isoflavones and coumestrol was analyzed. Soybean isoflavones were analyzed using Ultra Performance Liquid Chromatography (Acquity UPLC H-Class system, Waters). The isoflavones content showed an overall highly in the R5 stage, and the level was similar to that of no treatment in the R2 and R7 stage. The difference between the growth regulators was found to be higher than that of ethephon when ABA was treated. The coumestrol content was confirmed to be high in the order of R7, R5, and R2 on the treatment time, and it was found that the content increased as the treatment time was delayed. In the treatment with the growth regulator, the coumestrol content tended to be higher when ethephon was treated than ABA.

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Derivation of MSC Like-Cell Population from Feeder Free Cultured hESC and Their Proteomic Analysis for Comparison Study with BM-MSC (Feeder Free 상태에서 배양된 인간 배아 줄기세포를 이용한 중간엽 줄기세포 분화 및 단백체학을 이용한 골수 유래 중간엽 줄기세포와의 비교)

  • Park, Soon-Jung;Jeon, Young-Joo;Kim, Ju-Mi;Shin, Jeong-Min;Chae, Jung-Il;Chung, Hyung-Min
    • Reproductive and Developmental Biology
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    • v.34 no.3
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    • pp.143-151
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    • 2010
  • Pluripotency of human embryonic stem cell (hESC) is one of the most valuable ability of hESCs for applying cell therapy field, but also showing side effect, for example teratoma formation. When transplant multipotent stem cell, such as mesnchymal stem cell (MSC) which retains similar differentiation ability, they do not form teratoma in vivo, but there exist limitation of cellular source supply. Accordingly, differentiation of hESC into MSC will be promising cellular source with strong points of both hESC and MSC line. In this study, we described the derivation of MSC like cell population from feeder free cultured hESC (hESC-MSC) using direct differentiation system. Cells population, hESC-MSC and bone marrow derived MSC (BM-MSC) retained similar characteristics in vitro, such as morphology, MSC specific marker expression and differentiation capacity. At the point of differentiation of both cell populations, differentiation rate was slower in hESC-MSC than BM-MSC. As these reason, to verify differentially expressed molecular condition of both cell population which bring out different differentiation rate, we compare the molecular condition of hESC-MSC and BM-MSC using 2-D proteomic analysis tool. In the proteomic analysis, we identified 49 differentially expressed proteins in hESC-MSC and BM-MSC, and they involved in different biological process such as positive regulation of molecular function, biological process, cellular metabolic process, nitrogen compound metabolic process, macromolecule metabolic process, metabolic process, molecular function, and positive regulation of molecular function and regulation of ubiquitin protein ligase activity during mitotic cell cycle, cellular response to stress, and RNA localization. As the related function of differentially expressed proteins, we sought to these proteins were key regulators which contribute to their differentiation rate, developmental process and cell proliferation. Our results suggest that the expressions of these proteins between the hESC-MSC and BM-MSC, could give to us further evidence for hESC differentiation into the mesenchymal stem cell is associated with a differentiation factor. As the initial step to understand fundamental difference of hESC-MSC and BM-MSC, we sought to investigate different protein expression profile. And the grafting of hESC differentiation into MSC and their comparative proteomic analysis will be positively contribute to cell therapy without cellular source limitation, also with exact background of their molecular condition.

A Discrete Mathematical Model Applied to Genetic Regulation and Metabolic Networks

  • Asenjo, J.A.;Ramirez, P.;Rapaport, I.;Aracena, J.;Goles, E.;Andrews, B.A.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.3
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    • pp.496-510
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    • 2007
  • This paper describes the use of a discrete mathematical model to represent the basic mechanisms of regulation of the bacteria E. coli in batch fermentation. The specific phenomena studied were the changes in metabolism and genetic regulation when the bacteria use three different carbon substrates (glucose, glycerol, and acetate). The model correctly predicts the behavior of E. coli vis-a-vis substrate mixtures. In a mixture of glucose, glycerol, and acetate, it prefers glucose, then glycerol, and finally acetate. The model included 67 nodes; 28 were genes, 20 enzymes, and 19 regulators/biochemical compounds. The model represents both the genetic regulation and metabolic networks in an integrated form, which is how they function biologically. This is one of the first attempts to include both of these networks in one model. Previously, discrete mathematical models were used only to describe genetic regulation networks. The study of the network dynamics generated 8 $(2^3)$ fixed points, one for each nutrient configuration (substrate mixture) in the medium. The fixed points of the discrete model reflect the phenotypes described. Gene expression and the patterns of the metabolic fluxes generated are described accurately. The activation of the gene regulation network depends basically on the presence of glucose and glycerol. The model predicts the behavior when mixed carbon sources are utilized as well as when there is no carbon source present. Fictitious jokers (Joker1, Joker2, and Repressor SdhC) had to be created to control 12 genes whose regulation mechanism is unknown, since glycerol and glucose do not act directly on the genes. The approach presented in this paper is particularly useful to investigate potential unknown gene regulation mechanisms; such a novel approach can also be used to describe other gene regulation situations such as the comparison between non-recombinant and recombinant yeast strain, producing recombinant proteins, presently under investigation in our group.

Review of Ca Metabolic Studies and a Model for Optimizing Gastrointestinal Ca Absorption and Peak Bone Mass in Adolescents

  • Park, Jong-Tae;Cho, Byoung-Kwan;Lee, Wang-Hee
    • Journal of Biosystems Engineering
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    • v.40 no.1
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    • pp.78-88
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    • 2015
  • Purpose: The objective of this study is to review researches regarding factors that potentially affect adolescent calcium (Ca) metabolism, and to suggest a potential modeling approach for optimizing gastrointestinal Ca absorption and peak bone mass. Background: Optimal gastrointestinal Ca absorption is a key to maximizing peak bone mass in adolescents. Urine Ca excretion in adolescents rises only after bone accretion is saturated, indicating that higher intestinal Ca absorption and bone retention is necessary to ensure maximum bone accretion. Hence, maximizing peak bone mass is possible by controlling the factors influencing gastrointestinal Ca absorption and bone accretion. However, a mechanism that explains the unique adolescent Ca metabolism has not yet been elucidated. Review: Dietary factors that enhance gastrointestinal Ca absorption may increase the available Ca pool usable for bone accretion, and a specific hormone may direct optimal Ca utilization to maximize peak bone mass. IGF-1 is an endocrine hormone whose levels peak during adolescence and increase fractional Ca absorption and bone Ca accretion. Prebiotics, generally obtained from dietary sources, have been reported to exert a beneficial effect on Ca absorption via microbiota activity. We selected and reviewed three candidates that could be used to propose a comprehensive Ca metabolic model for optimal Ca absorption and peak bone mass in adolescents. Modeling: Modeling has been used to investigate Ca metabolism and its regulators. Herein, we reviewed previous Ca modeling studies. Based on this review, we proposed a method for developing a comprehensive model that includes regulatory effectors of IGF-1 and prebiotics.