• Title/Summary/Keyword: HSL

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Development of Inhibitors against TraR Quorum-Sensing System in Agrobacterium tumefaciens by Molecular Modeling of the Ligand-Receptor Interaction

  • Kim, Cheoljin;Kim, Jaeeun;Park, Hyung-Yeon;Park, Hee-Jin;Kim, Chan Kyung;Yoon, Jeyong;Lee, Joon-Hee
    • Molecules and Cells
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    • v.28 no.5
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    • pp.447-453
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    • 2009
  • The quorum sensing (QS) inhibitors that antagonize TraR, a receptor protein for N-3-oxo-octanoyl-L-homoserine lactones (3-oxo-C8-HSL), a QS signal of Agrobacterium tumefaciens were developed. The structural analogues of 3-oxo-C8-HSL were designed by in silico molecular modeling using SYBYL packages, and synthesized by the solid phase organic synthesis (SPOS) method, where the carboxamide bond of 3-oxo-C8-HSL was replaced with a nicotinamide or a sulfonamide bond to make derivatives of N-nicotinyl-L-homoserine lactones or N-sulfonyl-L-homoserine lactones. The in vivo inhibitory activities of these compounds against QS signaling were assayed using reporter systems and compared with the estimated binding energies from the modeling study. This comparison showed fairly good correlation, suggesting that the in silico interpretation of ligand-receptor structures can be a valuable tool for the pre-design of better competitive inhibitors. In addition, these inhibitors also showed anti-biofilm activities against Pseudomonas aeruginosa.

Mechanistic target of rapamycin and an extracellular signaling-regulated kinases 1 and 2 signaling participate in the process of acetate regulating lipid metabolism and hormone-sensitive lipase expression

  • Li, Yujuan;Fu, Chunyan;Liu, Lei;Liu, Yongxu;Li, Fuchang
    • Animal Bioscience
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    • v.35 no.9
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    • pp.1444-1453
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    • 2022
  • Objective: Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. Methods: The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 [ERK1/2] activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. Results: It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. Conclusion: Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition.

Size Distributions of Amphiboles in Soils from a Closed Asbestos Mine, Jecheon, Chungcheongbuk-do, Korea (충청북도 제천시 폐석면광산 주변 토양에서 검출되는 각섬석의 크기 분포)

  • Kwon, Jiwoon;Choi, Sung Won;Kim, Hyunwook
    • Economic and Environmental Geology
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    • v.47 no.5
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    • pp.497-505
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    • 2014
  • This study is for discrimination between asbestiform and non-asbestiform based on size characteristics of tremolite-actinolite fibers in soils from a closed asbestos mine, Jecheon, Chungcheongbuk-do, Korea. Soils and tremolite asbestos rocks were collected from a closed asbestos mine area. The dimensions of fibers with minimum $5{\mu}m$ in length and 3:1 in aspect ratio were measured using transmission electron microscopy (TEM) and compared to the known tremolite populations ranging from asbestiform to non-asbestiform. The geometric means of width of soils, asbestos rocks and National Institute for Standard and Technology (NIST) and Health and Safety Laboratory (HSL) reference samples were $1.2{\mu}m$, $0.3-0.6{\mu}m$, $1.3{\mu}m$ and $0.2{\mu}m$, respectively. The geometric means of aspect ratio of soils, asbestos rocks and NIST and HSL reference samples were 7.3, 13.7-30.1, 7.2 and 37.8, respectively. The population of tremolite-actinolite fibers from soils compared to known asbestiform and non-asbestiform tremolite was lack of thin and high aspect ratio fibers. Upper results suggest that tremolite-actinolite fibers in soils cannot be classified into a commercial grade asbestos. The tremolite-actinolite fibers do not mainly appear to be the result of contamination from distance asbestos sources by wind. For the management and control of asbestos in soils, size distributions of amphiboles should be incorporated into asbestos survey results of soils.

Lipolytic Effect of Supercritical Extraction from Pine Cone (Pinus koraiensis) in Mature 3T3-L1 Adipocytes (분화된 3T3-L1 세포에서 잣송이 초임계 추출물의 지방분해 효과)

  • Lee, Minhee;Nam, Da-Eun;Kim, Ok Kyung;Heo, Seok Hyun;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.9
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    • pp.1342-1348
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    • 2014
  • Seeds of Korean pine cone (Pinus koraiensis) have long been consumed as an edible food in countries located in North-East Asia, On the other hand, Korean pine cone, containing various polyphenols, is discarded as a useless garbage after removing seeds. This study investigated the lipolytic effects of pine cone extract in differentiated 3T3-L1 adipocytes. Intracellular lipid accumulation was measured by Oil red O staining, free glycerol release by colorimetric reaction, and expression of genes related to lipid metabolism by real-time PCR. Compared to control, pine cone extract reduced intracellular lipid accumulation by 8.8% and increased free glycerol release by 8.2% a concentration of $5{\mu}g/mL$ in differentiated 3T3-L1 adipocytes. mRNA levels of fatty acid synthesis were not significantly different between control and pine cone extract, but mRNA levels of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) significantly increased by 38.7% and 94.1% at a concentration of $5{\mu}g/mL$, respectively. Thus, pine cone extract is suggested to have lipolytic effects through induction of LPL and HSL gene expression.

Study on the Lipolytic Function of GPR43 and Its Reduced Expression by DHA

  • Sun, Chao;Hou, Zengmiao;Wang, Li
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.4
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    • pp.576-583
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    • 2009
  • G protein-coupled receptor 43 (GPR43) is a newly-discovered short-chain free fatty acid receptor and its functions remain to be defined. The objective of this study was to investigate the function of GPR43 on lipolysis. We successfully cloned the GPR43 gene from the pig (EU122439), and measured the level of GPR43 mRNA in different tissues and primary pig adipocytes. The expression level of GPR43 mRNA was higher in adipose tissue and increased gradually with adipocyte differentiation. Then we examined GPR43 mRNA level in different types, growth-stages and various regions of adipose tissue of pigs. The results showed that the expression level of GPR43 mRNA was significantly higher in adipose tissue of obese pigs than in lean pigs, and the expression level also gradually increased as age increased. We further found that the abundance of GPR43 mRNA level increased more in subcutaneous fat than visceral fat. Thereafter, we studied the correlation between GPR43 and lipid metabolism-related genes in adipose tissue and primary pig adipocytes. GPR43 gene had significant negative correlation with hormone-sensitive lipase gene (HSL, r = -0.881, p<0.01) and triacylglycerol hydrolase gene (TGH, r = -0.848, p<0.01) in adipose tissue, and had positive correlation with peroxisome proliferator-activated receptor $\gamma$ gene ($PPAR_{\gamma}$, r = 0.809, p<0.01) and lipoprotein lipase gene (LPL, r = 0.847, p<0.01) in adipocytes. In addition, we fed different concentrations of docosahexaenoic acid (DHA) to mice, and analyzed expression level changes of GPR43, HSL and TGH in adipose. The results showed that DHA down-regulated GPR43 and up-regulated HSL and TGH mRNA levels; GPR43 also had significant negative correlation with HSL (low: r = -0.762, p<0.01; high: r = -0.838, p<0.01) and TGH (low: r = -0.736, p<0.01; high: r = -0.586, p<0.01). Our results suggested that GPR43 is a potential factor which regulates lipolysis in adipose tissue, and DHA as a receptor of GPR43 might promote lipolysis through down-regulating the expression of GPR43 mRNA.

Verification of the Effect of Lemon Balm Extract on Triglyceride Control According to the Extraction Solvent (추출용매에 따른 레몬밤 추출물의 중성지방 조절 효능 검증)

  • Kim, Ji Youn;Kim, Kyoung Kon;Lee, Hye Rim;Kim, Dae Jung;Kim, Tae Woo
    • Korean Journal of Plant Resources
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    • v.35 no.2
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    • pp.372-379
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    • 2022
  • This study investigated the effect of lemon balm (Melissa officinalis) extract on improving blood triglycerides according to the extraction solvent using 3T3-L1 cells. Lemon balm was extracted with water (MOW100), 70% ethanol (MOE70), 50% ethanol (MOE50), and 30% ethanol (MOE30). To verify its efficacy on improving blood triglycerides, cell viability, lipid accumulation, triglyceride (TG) content, and expressions of protein kinase A (PKA), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), perilipin, and CGI-58 proteins were evaluated. Cytotoxicity was not evident up to an extract concentration of 1 mg/mL. Lipid accumulation and TG content were decreased in a concentration-dependent manner compared to their levels in the control group. When the MOW100 extract was applied at a concentration of 0.2 mg/mL, an inhibitory effect was evident, with lipid accumulation inhibited by 21.3% and TG content reduced by 32.7%. PKA phosphorylation and ATGL HSL and CGI-58 levels were increased. The data indicate that lemon balm extract obtained using water is more efficacious than extracted with ethanol. The aqueous extract shows potential in triglyceride control through lipolysis and lowering triglyceride levels.

The Regulation of Lipolysis in Adipose Tissue

  • Serr, Julie;Li, Xiang;Lee, Kichoon
    • Journal of Animal Science and Technology
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    • v.55 no.4
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    • pp.303-314
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    • 2013
  • Knowledge regarding lipid catabolism has been of great interest in the field of animal sciences. In the livestock industry, excess fat accretion in meat is costly to the producer and undesirable to the consumer. However, intramuscular fat (marbling) is desirable to enhance carcass and product quality. The manipulation of lipid content to meet the goals of animal production requires an understanding of the detailed mechanisms of lipid catabolism to help meticulously design nutritional, pharmacological, and physiological approaches to regulate fat accretion. The concept of a basic system of lipases and their co-regulators has been identified. The major lipases cleave triacylglycerol (TAG) stored in lipid droplets in a sequential manner. In adipose tissue, adipose triglyceride lipase (ATGL) performs the first and rate-limiting step of TAG breakdown through hydrolysis at the sn-1 position of TAG to release a non-esterified fatty acid (NEFA) and diacylglycerol (DAG). Subsequently, cleavage of DAG occurs via the rate-limiting enzyme hormone-sensitive lipase (HSL) for DAG catabolism, which is followed by monoglyceride lipase (MGL) for monoacylglycerol (MAG) hydrolysis. Recent identification of the co-activator (Comparative Gene Identification-58) and inhibitor [G(0)/G(1) Switch Gene 2] of ATGL have helped elucidate this important initial step of TAG breakdown, while also generating more questions. Additionally, the roles of these lipolysis-related enzymes in muscle, liver and skin tissue have also been found to be of great importance for the investigation of systemic lipolytic regulation.