• Title/Summary/Keyword: LPA

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Quantitative Analysis of Lysophosphatidic Acid in Human Plasma by Tandem Mass Spectrometry

  • Kim, Ho-Hyun;Yoon, Hye-Ran;Pyo, Dong-Jin
    • Bulletin of the Korean Chemical Society
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    • v.23 no.8
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    • pp.1139-1143
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    • 2002
  • Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and carrageenan/kaolin-induced arthritis in rats through LPAR2

  • Kim, Mijin;Sur, Bongjun;Villa, Thea;Yun, Jaesuk;Nah, Seung Yeol;Oh, Seikwan
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.575-582
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    • 2021
  • Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

HeLa E-Box Binding Protein, HEB, Inhibits Promoter Activity of the Lysophosphatidic Acid Receptor Gene Lpar1 in Neocortical Neuroblast Cells

  • Kim, Nam-Ho;Sadra, Ali;Park, Hee-Young;Oh, Sung-Min;Chun, Jerold;Yoon, Jeong Kyo;Huh, Sung-Oh
    • Molecules and Cells
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    • v.42 no.2
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    • pp.123-134
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    • 2019
  • Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals through specific G protein-coupled receptors, known as $LPA_{1-6}$. For one of its receptors, $LPA_1$ (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5'RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5' of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5' regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa E-box binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings.

Gintonin, a Panax ginseng-derived LPA receptor ligand, attenuates kainic acid-induced seizures and neuronal cell death in the hippocampus via anti-inflammatory and anti-oxidant activities

  • Jong Hee Choi;Tae Woo Kwon;Hyo Sung Jo;Yujeong Ha;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.390-399
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    • 2023
  • Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

A Study on the Impact of Elementary School Teachers' Perceptions of the School Library Roles on Their Library Use Behaviors (초등학교 교사의 학교도서관 역할 인식유형이 이용행태에 미치는 영향에 관한 연구)

  • Seungyeon Lee;Giyeong Kim
    • Journal of the Korean Society for information Management
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    • v.40 no.4
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    • pp.375-401
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    • 2023
  • A school library is where students develop their skills to cope with future uncertainty and can utilize various information materials to build their capability and response abilities to changes. Teachers' perception is crucial as their guidance is essential for the student to use the school library. Most studies, however, focused on quantitative measurement of the importance of the teachers' perception as an external environment, and there is a lack of specific categorization of different types of perceptions on the role of the school library. This study aims to examine types of perceptions about the school library among elementary school teachers. To do so, this study used Latent Profile Analysis (LPA), a person-centered approach, to identify teachers' complex perceptions about the role and importance of the school library, which were difficult to review in previous studies, and the teachers' most representative types of perceptions. Based on the findings from the above, this study is meaningful in proposing customized measures to operate and promote the school library depending on teachers' perceptions.

Atypical formations of gintonin lysophosphatidic acids as new materials and their beneficial effects on degenerative diseases

  • Ji-Hun Kim;Ra Mi Lee;Hyo-Bin Oh;Tae-Young Kim;Hyewhon Rhim;Yoon Kyung Choi;Jong-Hoon Kim;Seikwan Oh;Do-Geun Kim;Ik-Hyun Cho;Seung-Yeol Nah
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.1-11
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    • 2024
  • Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca2+]i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and antiarthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

A Study on Implementation and Performance Evaluation of Error Amplifier for the Feedforward Linear Power Amplifier (Feedforward 선형 전력증폭기를 위한 에러증폭기의 구현 및 성능평가에 관한 연구)

  • Jeon, Joong-Sung;Cho, Hee-Jea;Kim, Seon-Keun;Kim, Ki-Moon
    • Journal of Navigation and Port Research
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    • v.27 no.2
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    • pp.209-215
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    • 2003
  • In this paper. We tested and fabricated the error amplifier for the 15 Watt linear power amplifier for the IMT-2000 baseband station. The error amplifier was comprised of subtractor for detecting intermodulation distortion, variable attenuator for control amplitude, variable phase shifter for control phase, low power amplifier and high power amplifier. This component was designed on the RO4350 substrate and integrated the aluminum case with active biasing circuit. For suppression of spurious, the through capacitance was used. The characteristics of error amplifier measured up to 45 dB gain, $\pm$0.66 dB gain flatness and -15 dB input return loss. Results of application to the 15 Watt feedforward Linear Power Amplifier, the error amplifier improved with 27 dB cancellation from 34 dBc to 61 dBc IM$_3$.

Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors

  • Choi, Sun-Hye;Lee, Na-Eun;Cho, Hee-Jung;Lee, Ra Mi;Rhim, Hyewhon;Kim, Hyoung-Chun;Han, Mun;Lee, Eun-Hee;Park, Juyoung;Kim, Jeong Nam;Kim, Byung Joo;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.264-272
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    • 2021
  • Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

Effects of physical activity level on functional fitness in community-residing older adults (지역 거주 노인의 활동 체력과 신체 활동수준의 관련성)

  • Shin, So-Hee;Kim, Yong-An;Kim, Hyun-Soo
    • Journal of the Korea Convergence Society
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    • v.13 no.4
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    • pp.625-634
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    • 2022
  • The objective of this study was to examine the relationship between physical activity (PA) level and functional fitness (FF) parameters in community-dwelling older adults aged 65 or above in Korea. Subjects' (M: 1,645; F: 2,394) PA level were assessed using a questionnaire. The subjects were divided into two groups: one below the recommended level of PA(LPA) and one above the recommended level (PA). PA was further classified by intensity level into medium- and high-intensity PA (MIPA and HIPA respectively) groups. FF was assessed based on six test items representing the following fitness areas: lower and upper body strength, agility and dynamic balance, flexibility, aerobic capacity, coordination, and body composition. Of the subjects, 36% met the recommended level of PA. Both MIPA and HIPA were superior to LPA in all FF items(p<.05). The HIPA group was significantly better in terms of agility and dynamic balance, coordination, and lower body strength (only in women) than was the MIPA group(p<.05). In conclusion, PA above the recommended level is needed to maintain functional fitness. In addition, HIPA seems to promote fall-related functional fitness and should be encouraged when safe and feasible.