• Title/Summary/Keyword: trans acid

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Trans-10, cis-12 Conjugated Linoleic Acid Modulates Tumor Necrosis Factor-${\alpha}$ Production and Nuclear Factor-${\kappa}B$ Activation in RAW 264.7 Macrophages Through Formation of Reactive Oxygen Species (RAW 264.7 세포에 있어 t10c12-CLA의 ROS를 통한 TNF-${\alpha}$ 생산 및 NF-${\kappa}B$ 활성 조절)

  • Park, So-Young;Kang, Byeong-Teck;Kang, Ji-Houn;Yang, Mhan-Pyo
    • Journal of Veterinary Clinics
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    • v.31 no.6
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    • pp.469-476
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    • 2014
  • The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-naïve and LPS-stimulated RAW 264.7 macrophages and to examine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-${\alpha}$) production, and nuclear factor-kappa B (NF-${\kappa}B$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-${\alpha}$ in LPS-naïve RAW 264.7 cells. The CLA-induced TNF-${\alpha}$ production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-${\kappa}B$ and $PPAR{\gamma}$ in LPS-naïve RAW 264.7 cells, and this effect was abolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROS production. LPS increased both TNF-${\alpha}$ production and NF-${\kappa}B$ activity, whereas t10c12-CLA reduced TNF-${\alpha}$ production and NF-${\kappa}B$ activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production and NF-${\kappa}B$ activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ activation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected $PPAR{\gamma}$ activity in LPS-stimulated RAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-${\alpha}$ production by increasing ROS production in LPS-naïve RAW 264.7 cells, which is mediated by the enhancement of NF-${\kappa}B$ activity via $PPAR{\gamma}$ activation. By contrast, t10c12-CLA suppresses TNF-${\alpha}$ production by inhibiting ROS production and NF-${\kappa}B$ activation via a $PPAR{\gamma}$-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-${\alpha}$ production and NF-${\kappa}B$ activation through formation of ROS in RAW 264.7 macrophages.

Synthesis of Long-Chain Unsaturated Acetates (장직쇄상(長直鎖狀) 불포화(不飽和) 초산화합물(醋酸化合物)의 합성(合成)에 관(關)한 연구(硏究))

  • Oh, Sung-Ki
    • Applied Biological Chemistry
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    • v.19 no.1
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    • pp.1-23
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    • 1976
  • The female moths of Lepidoptera comprising over 1,000,000 described species possess long-chain unsaturated alcohols or esters as the typical structure of potential sex attractants. In this experiment, various stereoisomers of $C_{16}-unsaturated$ acetates were synthesized for potential sex attractants; e.g., $CH_3(CH_2)_mCH=CH(CH_2)_nOR$ (m=0-12, n=1-13, R=H and $-COCH_3$). Seventeen acetates were spectrometrically examined so that the data would provide a ready catalog of gas chromatography and mass spectrometric data for comparison with natural insect sex attractants. Exclusively cis and trans isomers were obtained by the catalytic and chemical reduction methods, respectively. Commercially available $CH_3(CH_2)_mBr,\;CH_3(CH_2)_mC{\equiv}CH,\;HC{\equiv}C(CH_2)_nOH\;and\;HO(CH_2)_n\;OH$ were used for the synthetic starting material. 1-Alkynes, $CH_3(CH_2)_m\;C{\equiv}CH$ exceeding nine methylene groups did not condense with alkyl dihalides. The yield of coupling products was gradually decreased with increasing the molecular weight of diols. In the coupling reaction of $BrCH_2CH_2$ OTHP with acetylene gas, the tetrahydropyranyl ether of bromohydrin produced undesirable elimination product. In this experiment, it seems that p-toluenesulfonic acid is greatly favoured hydrolyzing agent over dilute sulfuric acid in the hydrolysis of the tetrahydropyranyl ether of long-chain alkynols.

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Comparison of the Nutritional Composition for Bokkeumbap Products in High-Frequency Processed Foods in the Republic of Korea (국내 다빈도 가공식품 중 볶음밥류의 영양성분 함량 비교)

  • Jung, Ui-Hwan;Cha, Seung-Hyeon;Kim, Byung Hee;Yoon, Sung-Won;Kim, In Hwan;Chun, Jiyeon;Lee, Ki-Teak;Kim, Younghwa;Shin, Eui-Cheol;Seo, Dongwon;Lee, Sam-Pin;Lee, Junsoo;Jang, Keum-Il
    • The Korean Journal of Food And Nutrition
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    • v.32 no.6
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    • pp.589-597
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    • 2019
  • In this study, 70 kinds of nutritional composition for five bokkeumbap products(spicy chicken, shrimp(saeu), haemul, nakji, and barbecue bokkeumbap) in high-frequency processed foods were analyzed. Raw data of intake amounts were collected from the 7th Korea National Health and Nutrition Examination Survey. Regarding proximate composition, spicy chicken bokkeumbap had lower water content and higher carbohydrate content than other bokkeumbaps, resulting in the highest total calories. The proximate composition of other bokkeumbaps were all distributed within a similar range. Vitamin content differed according to ingredients added to the bokkeumbaps. Haemul bokkeumbap had high content of vitamins B1 and B2, nakji bokkeumbap had high content of vitamin C and β-carotene, and barbecue bokkeumbap had high content of total niacin, folic acid, and vitamin A. For mineral content, barbecue bokkeumbap showed the highest content distribution, while nakji bokkeumbap showed the lowest content distribution. Regarding fatty acid and fat content, the highest content of fatty acids, saturated fats, and trans fats was detected in shrimp(saeu) bokkeumbap. For amino acid content, barbecue bokkeumbap showed highest content distribution. These results can be used as salient basic data for a food nutrient composition database and to significantly contribute to consumers' health.

Dietary Effect of Silk Protein Sericin or Fibroin on Plasma and Epidermal Amino Acid Concentration of NC/Nga Mice (실크 단백질 Sericin 및 Fibroin의 식이 공급이 아토피 피부염 동물 모델 NC/Nga Mice의 혈장과 표피의 유리 아미노산 함량에 미치는 영향)

  • Kim, Hyun-Ae;Park, Kyung-Ho;Yeo, Joo-Hong;Lee, Kwang-Gili;Jeong, Do-Hyeon;Kim, Sung-Han;Cho, Yun-Hi
    • Journal of Nutrition and Health
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    • v.39 no.6
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    • pp.520-528
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    • 2006
  • Free amino acids in epidermis function as a major component of Natural Moisturizing Factor (NMF), which maintains the optimal level of water in skin even at the low humidity. In fact, the depletion of free amino acids is reported in the epidermis of atopic dermatitis, the skin condition involving dryness. As an effort searching the dietary source for improving the level of water and free amino acid in epidermis, the dietary effects of silk protein, sericin (S) and fibroin (F) on trans epidermal water loss (TEWL), and plasma and epidermal levels of free amino acids were compared in this study. Thirty of male NC/Nga mice, an animal model of atopic dermatitis, were divided into three groups: group CA as an atopic control with control diet, group S: 1% sericin diet and group F: 1% fibroin diet. Ten of male BALB/c mice were served as group C (control group) with control diet. All mice were fed on diet and water ad libitum for 10weeks. Dry skin condition was established in group CA as TEWL was increased (148.7% of group C). In parallel, epidermal level of glutamate, one of major amino acids functioning as NMF, was dramatically decreased and epidermal levels of methionine and alanine were inversely elevated. Dietary supplementation of sericin (group S) reduced TEWL at the similar level with group C and increased epidermal levels of glutamate as well as serine and glycine, the other major amino acids as NMF. Despite a marked decrease of methionine and alanine, the reduction of TEWL and epidermal levels of glutamate, serine and glycine of group F were less than of group S. Furthermore, in contrast to similar levels of other free amino acids in plasma and epidermis of group S and group C, plasma and epidermal levels of other free amino acids, specifically phenylalanine, isoleucine, cysteine and tyrosine in epidermis of group F, were significantly higher than of group C. Together, our data demonstrate that dietary supplementation of sericin is more effective at improving dry skin condition that paralleled with the normalization of free amino acids in plasma and epidermis of NC/Nga mice.

Effect of retinoic acid on the radiosensitivity of normal human oral keratinocyte (Retinoic acid가 사람 정상 구강각화세포의 방사선감수성에 미치는 영향에 관한 연구)

  • Lee Jean;Heo Min-Suk;Lee Sam-Sun;Oh Sung-Ook;Lee Sul-Mi;Choi Hang-Moon;Choi Soon-Chul;Park Tae-Won
    • Imaging Science in Dentistry
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    • v.33 no.2
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    • pp.97-105
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    • 2003
  • Purpose : To evaluate the effect of all-trans-retinoic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). Materials and methods: Relative cell survival fraction including SF2 (survival fraction at 2 Gy) was calculated on the basis of colony formation assay. Data were fitted to the linear-quadratic model to establish the survival curve and calculate α and β values. Using flow cytometry at 1, 2, 3, 4, and 5 days after exposure to 2 and 10 Gy irradiation, cell cycle arrest and apoptosis were analysed. To understand the molecular mechanism of the radiosensitization of ATRA on NHOK, proteins related with apoptosis and cell cycle arrest were investigated by Western blot analysis. Results: Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased α and β value, indicating that ATRA increased radiosensitivity of NHOK. ATRA increased LDH significantly, but increasing irradiation dose decreased LDH, suggesting that the radiosensitizing effect of ATRA is not directly related with increasing cell necrosis by ATRA. ATRA did not induce appotosis but increased G2 arrest after 10 Gy irradiation, implying that the increased radiosensitivity of NHOK may be due to a decrease in mitosis casued by increasing G2 arrest. ATRA inhibited the reduction of p53 at 3 days after l0Gy irradiation and increased p21 at 1 day after 10 Gy irradiation. Further study is required to determine the precise relationship between this effect and the radiosensitizing effect of A TRA. Conclusion: These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.

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Study on Temperature Dependence of Molecular Structure in Stearic Acid LB Films Using FTIR-RAS (FTIR-RA 분광법을 이용한 스테아르산 단분자막에서 분자구조의 온도의존성 고찰)

  • Kim, Dong Won;Park, Sang Rae;Umemura Junjo;Takeda Satoshi;Hasegawa Takeshi;Takenaka Tohru;Lee Hai Won
    • Journal of the Korean Chemical Society
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    • v.37 no.6
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    • pp.570-576
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    • 1993
  • 1-, 3-, 9-, and 21-Monolayer Langmuir-Blodgett(LB) films of stearic acid were deposited on silver-coated glass slides at the surface pressure of 30 mN/m. Fourier transform infrared(FTIR) reflection-absorption spectra (RAS) of these LB films were recorded at various temperatures from 31 to $72^{\circ}C.$ The spectra at $31^{\circ}C$ exhibited characteristic features of highly perpendicular orientation of the hydrocarbon chain. In the 1-monolayer LB film, the C=O stretching band was not observed, presumably due to the image dipole effect on the silver surface. In the 1-and 3-monolayer LB films, the trans isomer of stearic acid was prominent, but the cis isomer was dominant in the 21-monolayer LB film. FTIR-RAS measurements at an elevated temperature indicated that the chain melting temperature increases and approached to the bulk melting point with increasing the number of monolayer, except for the 1-monolayer LB film which has a higher melting temperature than the 3-monolayer film due to the strong interaction with the silver substrate.

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Moisturizing Effects and Composition Analysis of Proteoglycan Isolated from Chia (Salvia hispanica) Seed (치아 씨앗으로부터 분리한 단백다당체의 성분분석과 보습 효과)

  • Lee, Bum-Chun;Joo, Chul-Gue;Hur, Ji-Yeon;Lee, Keun-Ha;Kim, Young-Jin;Lee, Chan-Woo;Kim, Jin-Woong;Park, Yong-Il;Kim, Hyun-Sook;Choe, Tae-Boo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.36 no.2
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    • pp.121-128
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    • 2010
  • We investigated the effects of skin hydration and composition analysis of proteoglycan (chia seed polymer) produced from chia (Salvia hispanica) seed. The result showed that proteoglycan of chia seeds is composed of galactose (46.8 %), glucuronic acid (27.1 %), rhamnose (8.7 %), xylose (7.6 %), glucose (4.9 %), fructose (2.3 %), mannose (1.8 %), arabinose (0.9 %) and the amount of proteins contained is 31.3 mg/g with the constituent amino acid compositions (mg/g) of Asp (1.9), Glu (3.6), Ser (0.9), Gly (3.6), Thr (0.8), Arg (1.0), Ala (2.0), Tyr (0.4), Cys (4.8), Val (1.1), Phe (0.5), Ile (0.6), Leu (0.9). The molecular weight of the proteoglycan measured by GPC (Gel Permeation Chromatography) is the range of 100,000~250,000 Da and the average molecular weight is 170,000 Da. The moisturizing effects and trans-epidermal water loss (TEWL) of chia seed polymer in cosmetic products (O/W emulsion) were studied in vivo. Chia seed polymer showed good skin hydration effects when compared with sodium hyaluronate which is a common moisturizer. Taken all together, chia seed polymer should be a very useful cosmetic ingredient as a moisturizer and a protecting agent from various skin irritations.

Comparison of miR-106b, miR-191, and miR-30d expression dynamics in milk with regard to its composition in Holstein and Ayrshire cows

  • Marina V. Pozovnikova;Viktoria B. Leibova;Olga V. Tulinova;Elena A. Romanova;Artem P. Dysin;Natalia V. Dementieva;Anastasiia I. Azovtseva;Sergey E. Sedykh
    • Animal Bioscience
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    • v.37 no.6
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    • pp.965-981
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    • 2024
  • Objective: Milk composition varies considerably and depends on paratypical, genetic, and epigenetic factors. MiRNAs belong to the class of small non-coding RNAs; they are one of the key tools of epigenetic control because of their ability to regulate gene expression at the post-transcriptional level. We compared the relative expression levels of miR-106b, miR-191, and miR-30d in milk to demonstrate the relationship between the content of these miRNAs with protein and fat components of milk in Holstein and Ayrshire cattle. Methods: Milk fat, protein, and casein contents were determined in the obtained samples, as well as the content of the main fatty acids (g/100 g milk), including: saturated acids, such as myristic (C14:0), palmitic (C16:0), and stearic (C18:0) acids; monounsaturated acids, including oleic (C18:1) acid; as well as long-, medium- and short-chain, polyunsaturated, and trans fatty acids. Real-time stem-loop one-tube reverse transcription polymerase chain reaction with TaqMan probes was used to measure the miRNA expression levels. Results: The miRNA expression levels in milk samples were found to be decreased in the first two months in Holstein breed, and in the first four months in Ayrshire breed. Correlation analysis did not reveal any dependence between changes in the expression level of miRNA and milk fat content, but showed a multidirectional relationship with individual milk fatty acids. Positive associations between the expression levels of miR-106b and miR-30d and protein and casein content were found in the Ayrshire breed. Receiver operating characteristic curve analysis showed that miR-106b and miR-30d expression levels can cause changes in fatty acid and protein composition of milk in Ayrshire cows, whereas miR-106b expression level determines the fatty acid composition in Holsteins. Conclusion: The data obtained in this study showed that miR-106b, miR-191, and miR-30d expression levels in milk samples have peculiarities associated with breed affiliation and the lactation period.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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Effect of retinoic acid on the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase (Herpes Simplex Virus thymidine kinase gene을 이용한 유전자 치료에서 retinoic acid가 bystander effect에 미치는 영향)

  • Park, Jae Yong;Kim, Chang Ho;Jung, Tae Hoon;Albelda, Steven M.
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.1
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    • pp.162-174
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    • 1997
  • Background : Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase/ganciclovir (HSVtk) "prodrug" system. Since retinoids have been reported to increase GJIC by induction of connexin 43 expression, we hyporthesized that treatment of tumor cells with retinoic acid could augment the bystander effect of the HSVtk/GCV system and result in improved tumor cell killing by enhancing GJIC. Methods : We transferred HSVtk gene to SKHep-J cell line that does not express connexin43, and also transferred the gene to human and murine mesothelioma cell lines that express connexin43. We verified that retinoic acid enhanced GJIC utilizing a functional double-dye transfer study and evaluated the effects of retinoic acid on the growth rate of tumor cells. We then tested the effects of retinoic acid on bystander-mediated cell killing. Results : Addition of all-trans retinoic acid (RA) increased GJIC in cell lines expressing connexin 43 and was asspciated with more efficient in vitro bystander killing in cells transduced with HSVtk via adenoviral and retroviral vectors. In contrast, there was no increase in the efficiency of the bystander effect after exposure to RA in a cell line which had no delectable connexin 43. Conclusion : These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effect and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk system to treat tumors.

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