• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.361-377
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• 2024

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aβ_1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of AE and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1437-1447
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• 2023

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

• Development and Reproduction
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• v.12 no.1
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• pp.19-30
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• 2008

Proper development of fertilized oocyte to blastocyst is a key step in mammalian development to implantation. During development of preimplantation embryos, the mammalian embryo needs supply the energy substrate for keep viability. Usually mammalian oocyte get substrate especially energy substrate from oviduct and uterus, because it does not store much substrate into cytoplasm during oogenesis. Carbohydrates are known as a main energy substrate for preimplantation stage embryos. Glucose, lactate and pyruvate are essential component in preimplantation embryo culture media and there are stage specific preferences to them. Glucose transporter and $H^+$-monocarboxylate cotransporter are a main mediator for carbohydrate transport and those expression levels are primarily under the control of intrinsic or extrinsic factors like insulin and glucose. Other organic substances, amino acids, lipids and nucleotides are used as energy substance and cellular regulation factor. Though since 1960s, successful development of fertilized embryo to blastocyst has been accomplished with chemically defined medium for example BWW and give rise to normal offspring in mammals, the role of metabolites and the regulation of intermediary metabolism are still poorly understood. Glucose may permit expression of metabolic enzymes and transporters in compacting morula, capable of generating the energy required for blastocyst formation. In addition, it has been suggested that the cytokines can modulate the metabolic rate of carbohydrate in embryos and regulate the preimplantation embryonic development through control the metabolic rate. Recently we showed that lactate can be used as a mediator for preimplantation embryonic development. Those observations indicate that metabolites of carbohydrate are required by the early embryo, not only as an energy source, but also as a key substrate for other regulatory and biosynthetic pathways. In addition metabolites of carbohydrate may involve in cellular activity during development of preimplantation embryos. It is suggested that through these regulation and with other regulation mechanisms, embryo and uterus can prepare the embryo implantation and further development, properly.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.15-21
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• 2021

Purpose: Urea cycle disorder (UCD) is an inherited inborn error of metabolism, acting on each step of urea cycle that cause various phenotypes. The purpose of the study was to investigate the long-term clinical consequences in different groups of UCD to characterize it. Methods: Twenty-two patients with UCD genetically confirmed were enrolled at Pusan National University Children's hospital and reviewed clinical features, biochemical and genetic features retrospectively. Results: UCD diagnosed in the present study included ornithine transcarbamylase deficiency (OTCD) (n=10, 45.5%), argininosuccinate synthase 1 deficiency (ASSD) (n=6, 27.3%), carbamoyl-phosphate synthetase 1 deficiency (CPS1D) (n=3, 13.6%), hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS) (n=2, 9.1%), and arginase-1 deficiency (ARG1D) (n=1, 4.5%). The age at the diagnosis was 32.7±66.2 months old (range 0.1 to 228.0 months). Eight (36.4%) patients with UCD displayed short stature. Neurologic sequelae were observed in eleven (50%) patients with UCD. Molecular analysis identified 37 different mutation types (14 missense, 6 nonsense, 6 deletion, 6 splicing, 3 delins, 1 insertion, and 1 duplication) including 14 novel variants. Progressive growth impairment and poor neurological outcomes were associated with plasma isoleucine and leucine concentrations, respectively. Conclusion: Although combinations of treatments such as nutritional restriction of proteins and use of alternative pathways for discarding excessive nitrogen are extensively employed, the prognosis of UCD remains unsatisfactory. Prospective clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth or neurological outcomes and decrease metabolic crisis episodes in patients with UCD.

• Journal of Life Science
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• v.34 no.7
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• pp.465-475
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• 2024

Lactiplantibacillus plantarum K9 is a probiotic strain that can be utilized from various bioactive substances isolated from Protaetia brevitarsis seulensis larvae. In this study, a genetic analysis of L. plantarum K9 revealed the existence of a bacterial chromosome and three plasmids. The glycolysis pathway and pentose phosphate pathway were examined for their normal functioning via an analysis of the core metabolic pathways of L. plantarum K9. Since the key enzymes, fluctose-1,6-bisphospatase (EC: 3.1.3.11) and 6-phosphogluconate dehydratase (EC: 4.2.1.12)/2-keto-deoxy-6-phosphogluconate (KDPG) aldolase (EC: 4.2.1.55), of gluconeogenesis and the ED pathway were not identified from the L. plantarum K9 genome, we suggest that gluconeogenesis and the ED pathway are not performed in L. plantarum K9. Additionally, while some enzymes, related to fumarate and malate biosyntheses, involved in the TCA cycle were identified from L. plantarum K9, the enzymes associated with the remaining TCA cycle were absent, indicating that the TCA cycle cannot proceed. Meanwhile, based on our findings, we propose that the oxidative electron transport system performs class IIB-type (bd-type) electron transfer. In summary, we assert that L. plantarum K9 performs homolactic fermentation, executes gluconeogenesis and the pentose phosphate pathway, and carries out energy metabolism through the class IIB-type oxidative electron transport system. Therefore, we suggest that L. plantarum K9 has relatively high lactic acid production, and that it has excellent antibacterial activity, as a result, compared to other lactic acid bacterial strains. Moreover, we speculate that L. plantarum K9 has an oxidative electron transport capability, indicating that it is highly resistant to oxygen and suggesting that it has fine cultivation characteristics, which collectively make it highly suitable for use as a probiotic.

• Journal of Life Science
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• v.28 no.9
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• pp.999-1006
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• 2018

Obesity is epidemic worldwide and has reportedly been linked to the progression of several metabolic and cardiovascular diseases. The natural products are decreasing the side effects of medicines used for obesity and also have health benefits dut to their numerous bioactive compounds. In this context, Artemisia scoparia is a widespread plant that has been suggested as possessing various types of bioactivity. In this study, the crude extract from A. scoparia (ASE) was tested for its ability to suppress adipogenesis in mouse 3T3-L1 pre-adipocytes. The molecular pathway by which ASE affects differentiation of 3T3-L1 cells was also investigated. The introduction of ASE to differentiating 3T3-L1 pre-adipocytes resulted in suppressed adipogenesis, as confirmed by decreased intracellular lipid accumulation. The differentiating cells treated with 10 and $100{\mu}g/ml$ of ASE showed 21.9 and 29.0% less lipid accumulation, respectively, than untreated adipocytes. In addition, the results indicated that ASE treatment lowered the expression of the adipogenesis-related factors $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP-1c. Furthermore, treating with ASE notably decreased levels of phosphorylated p38, ERK, and JNK in 3T3-L1 adipocytes. These results indicate that ASE exhibits significant anti-adipogenesis activity by downregulating the MAPK and $PPAR{\gamma}$ pathways during the differentiation of 3T3-L1 pre-adipocytes. Therefore, A. scoparia may be a potential source of natural products against obesity.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04a
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• pp.69-75
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• Journal of Microbiology and Biotechnology
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• v.21 no.4
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• pp.366-373
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• 2011

We characterized the proteomes of murine N2a cells following infection with three rabies virus (RV) strains, characterized by distinct virulence phenotypes (i.e., virulent BD06, fixed CVS-11, and attenuated SRV9 strains), and identified 35 changes to protein expression using two-dimensional gel electrophoresis in whole-cell lysates. The annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. Specifically, a-enolase, prx-4, vimentin, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and prx-6 were significantly up-regulated, whereas Trx like-1 and galectin-1 were down-regulated following infection of N2a cells with all three rabies virus strains. However, comparing expressions of all 35 proteins affected between BD06-, CVS-11-, and SRV9-infected cells, specific changes in expression were also observed. The up-regulation of vimentin, CIAPIN1, prx-4, and 14-3-3 ${\theta}/{\delta}$, and down-regulation of NDPK-B and HSP-1 with CVS and SRV9 infection were ${\geq}2$ times greater than with BD06. Meanwhile, Zfp12 protein, splicing factor, and arginine/serine-rich 1 were unaltered in the cells infected with BD06 and CVS-11, but were up-regulated in the group infected with SRV9. The proteomic alterations described here may suggest that these changes to protein expression correlate with the rabies virus' adaptability and virulence in N2a cells, and hence provides new clues as to the response of N2a host cells to rabies virus infections, and may also aid in uncovering new pathways in these cells that are involved in rabies infections. Further characterization of the functions of the affected proteins may contribute to our understanding of the mechanisms of RV infection and pathogenesis.

• Korean Journal of Weed Science
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• v.16 no.2
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• pp.160-170
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• 1996

Several physiological responses were investigated in plants treated with TOPE as a preliminary step to know its action site. Unlike photo-dependent diphenylethers, herbicidal activity of TOPE appeared slowly and its typical symptoms were both burning of leaf blades and abnormal division of meristem in grasses, Similarly, both leakage of cell electrolytes and the curling of cotyledon margin were also shown in cucumber(Cucumis sativus L.). Biosynthesis of chlorophyll in etiolated cucumber cotyledon was not inhibited directly by treatment of TOPE at low light intensity(5.5${\mu}$ mol $m^{-2}s^{-1}$ PAR) and protoporphyrin IX was not also accumulated. The contents of phytoene, phytofluene and ${\beta}$-carotene were abnormaly increased. Photosynthesis was inhibited only at high concentration. Mitochondrial respiration was inhibited at high concentration but rather increased significantly at 10${\mu}$M of TOPE. However, respiration inhibitors did not alleviate the two symptoms of TOPE in cucumber cotyledon. In the same experiments, using inhibitors of protein or nucleic acid biosynthesis, only one of the two symptoms was alleviated by chloramphenicol and cycloheximide. In contrast, both symptoms were alleviated by actinomycin-D and hydroxyurea, suggesting that nucleic acid metabolism might be preferentially related to the mode of action of TOPE. DNA, RNA and protein contents were accumulated in both cucumber cotyledon and rice (Oryza sativa L.) routs treated with TOPE, and the DNA of them was increased at first. Thus, it is conjectured that TOPE increase nucleic acid metabolism directly or indirectly, and then disturb various metabolic pathways causing abnormal physiological and morphological effects followed by final death.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.5
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• pp.1099-1106
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• 1999

Effects of dietary carotenoids were investigated on metabolism of the carotenoids, and body pigmen tation in oily bittering, Acheilognathus koreensis. Two weeks later after depletion,oily bitterings were fed the diets supplemented with either lutein, cynthiaxanthin and astaxathin for 4 weeks. Carotenoids distributed to and metabolized in integument were analyed. The carotenoid isolated from the integument of wild oily bittering, composed of 47.2% zeaxanthin, 11.4% lutein epoxide, 11.0% diatoxanthin, 9.7% lutein and 8.3% zeaxanthin epoxide. Meanwhile, two weeks later after depletion, the carotenoid composed of 29.9% crytoxanthin, 19.3% zeaxanthin, 13.2% lutein epoxide, 12.0% diatoxanthin and 8.8% zeaxanthin epoxide. These indicated that zeaxanthin, diatoxanthin, lutein epoxide and zeaxanthin epoxide were actively metabolized in oily bittering, compared to that of other fresh water fish. Total carotenoid content in the integument of wild oily bittering and oily bittering depleted for two weeks was found to be 1.72mg% and 2.08mg%, respectively. Two weeks later after treatment of experimental diet, total carotenoids content was increased to 2.23mg% in lutein, 2.36mg% in cynthiaxanthin and 2.49mg% in astaxanthin supplemented group, which were relatively higher than 2.10mg% in control group. Meanwhile, 4 weeks later, total ca rotenoids content was decreased to 1.76mg% in control, 1.95mg% in lutein, 1.74mg% in cynthiaxanthin and 1.72mg% in astaxanthin supplemented groups. These result indicate that dietary carotenoids were rapidly accumulated and then metabolized to certain metabolites shortly after feeding. Body pigmentation effects of the carotenoids due to accumulation of carotenoids in the integument of oily bittering was the most effectively shown in the astaxanthin supplemented group, followed by cynthiaxanthin and lutein supplemented groups. In the integument of oily bittering, dietary carotenoids were presumably biotrans formed via either oxidative or reductive pathways as presumed the variation of total carotenoid content and carotenoid composition in all experimental groups. The lutein was oxidized either to astaxanthin via doradexanthin and doradexanthin, or to zeaxanthin epoxide via zeaxanthin by oxidative pathway. Cynthiaxanthin was converted either to diatoxanthin and zeaxanthin by reductive pathway and then to zeaxanthin epoxide by oxidative pathway, or it was converted to astaxanthin via diatoxanthin, zeaxan thin and doradexanthin by oxidative pathway. Astaxanthin was converted to doradexanthin and zeaxanthin by reductive pathway and then to zeaxanthin epoxide by oxidative pathway. These results suggest that, oxidative pathway of carotenoids was major metabolic pathway along with reductive path way in fresh water fish.