• 제목/요약/키워드: $LPA_1$

검색결과 107건 처리시간 0.024초

Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

  • Choi, Sun-Hye;Lee, Byung-Hwan;Kim, Hyeon-Joong;Jung, Seok-Won;Kim, Hyun-Sook;Shin, Ho-Chul;Lee, Jun-Hee;Kim, Hyoung-Chun;Rhim, Hyewhon;Hwang, Sung-Hee;Ha, Tal Soo;Kim, Hyun-Ji;Cho, Hana;Nah, Seung-Yeol
    • Molecules and Cells
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    • 제37권9호
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    • pp.656-663
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    • 2014
  • Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits $[Ca^{2+}]_i$ transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier $K^+$ ($I_{Ks}$) channel is a cardiac $K^+$ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating $I_{Ks}$ channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human $I_{Ks}$ channel activity by expressing human $I_{Ks}$ channels in Xenopus oocytes. We found that gintonin enhances $I_{Ks}$ channel currents in concentration- and voltage-dependent manners. The $EC_{50}$ for the $I_{Ks}$ channel was $0.05{\pm}0.01{\mu}g/ml$. Gintonin-mediated activation 1 of the $I_{Ks}$ channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an $IP_3$ receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the $I_{Ks}$ channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 $[Ca^{2+}]_i$/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on $I_{Ks}$ channel. However, gintonin had no effect on hERG $K^+$ channel activity. These results show that gintonin-mediated enhancement of $I_{Ks}$ channel currents is achieved through binding of the $[Ca^{2+}]_i$/CaM complex to the C terminus of KCNQ1 subunit.

새로운 파일롯 신호 인가 기법을 이용한 피드포워드 선형증폭기의 설계 (Design of Feedforward Linear Power Amplifier using Novel Injection Method of a Pilot Signal)

  • 이경희;박웅희;강상기
    • 한국전자파학회논문지
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    • 제13권10호
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    • pp.998-1004
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    • 2002
  • 본 논문은 하나의 파일롯 신호를 이용하여 다중 캐리어를 수용하는 IMT-2000 전 대역에서 동작하는 중계기용 Feedforward 선형증폭기의 설계 및 제작에 관한 것이다. 본 논문에서 제시한 방법은 기존에 나와있는 파일롯 신호 인가 방법과는 달리 하나의 파일롯 신호를 분기하여 첫번째 루프(혼변조 신호 추출 루프)와 두번째 루프(혼변조 신호 제거 루프)에 인가함으로써, 증폭기에 입력되는 입력신호의 주파수와 레벨의 변화에 따라 자동 적응적으로 혼변조 신호들을 제거하도록 설계하였다. 제작 결과 2110 MHz - 2170 MHz 주파수 범위에서 최종 출력이 20 W$_{avg}$ 일 때 임의의 20 MHz에서 IMD 특성이 -60 dBc 이하가 됨으로써 20 dB 이상을 개선시켰으며 제안된 선형증폭기는 중계기의 다중캐리어 선형증폭기로서 적합함을 확인하였다.

1.9 GHZ PCS 기지국용 선형 전력증폭기의 제작 (Implementation of Linear Power Amplifier with 1.9 GHz for PCS Basestation)

  • 김상기;방성일
    • 전기전자학회논문지
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    • 제7권1호
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    • pp.88-96
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    • 2003
  • 본 논문에서는 미국내의 상용 PCS 서비스 대역인 $1.9GHz(1.93{\sim}1.99GHz)$대역에서 사용 가능한 선형 전력 증폭기를 설계 및 제작하였다. 실제로 제작한 선형 전력 증폭기는 출력이 25W이고 Feedforward선형화 기법을 사용하여 FCC가 규정한 혼변조 왜곡 특성을 만족하도록 하였다. 선형 전력 증폭기의 출력별로 측정한 결과 1W(30dBm)에서 25W(44dBm)까지 14dB의 측정구간에서 선형화에 의한 혼변조 왜곡은 최저 10.51dBc부터 최고 19.01dBc까지 개선되었고, 최종 출력에서의 IMD 레벨은 최저 64.84dBc에서 최고 68.17dBc로 각각 나타났다. 이러한 특성은 PCS 기지국의 상용제품으로 충분히 사용할 수 있을 것으로 기대된다.

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폐동맥 면적지표가 청색증 심장 기형에 있어서 라스텔리씨 수술후 조기 예후 판정에 미치는 영향 (Pulmonary artery index as a predictor of early postoperative result and a critrion for rastelli operation of cyanotic congenital heart disease)

  • 김진국;노준량
    • Journal of Chest Surgery
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    • 제21권6호
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    • pp.957-969
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    • 1988
  • There is tendency of increasing number and decreasing age of patients who are indicated for Rastelli operation for their cyanotic congenita heart disease. So there is the need to find the creiterion which saves the patients from early postoperative hemodynamic disturbances. We reviewed the 26 patients who had been performed Rastelli operation at Seoul national University hOipital from January 1981 to June 1988. mean age of the patients was 7.8 $\pm$ 3.4 years (range 2.5-1.5 years), mean body surface area(BSA) 0.79 $\pm$ 0.25 $m^{2}$(range 0.49-1.51 $m^{2}$) and mean hematocrit 57.95 $\pm$ 12%(range 48-80%). We diveded these patients into survived group and died group before postoperative 72 hours, and analysed preoperative arterial oxygen saturation($SaO_{2}$), the ratio of diameter of fight pulmonary artery to ascending aorta(RA:/AA), the ratio of both right and left pulmonary artery diameter to descending thoracic aorta(RPA+LPA/DTA), pulmonary artery index(PA index), cardiopulmonary bypass time, aorta cross-clamping time, postoperative perfusion state and total amount of dopamine infused postoperatively. The results showed that RPA+LPA/DTA and PA index were statistically significatn factors to influence early postoperative cardiac death rate (P<0.05). Especially there were good linear correlations between PA index(X) and perpheral perfusion index(Y)(Y = -1.15 + 0.02 X, r = 0.86, P<0.01) and between PA index(X) and total amount of dopamine infused before postoperative 72 hours(mg/kg, Y)(Y = 61.94 - 0.15 X, r = - 0.80, P<0.01). Also there were tendencies that the higher RPA + LPA/DTA(Y), the betterperipheral perfusion (X) and the lower need of dopamine(X), but no statistical significance. (Y = 0.78 + 1.60 X, r = 0.49, P>0.05) And the discrimant analysis showed that patients with PA index over 221 $mm^{2}$/BSA could undergo correction with 25 per cent of error rate. In conclusion, early postoperative hemodynamic states could be predicted by preoperatively measured PA index, and which can be used as a criterion for Rastelli operation performed on cyanotic congenital heart disease.

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The role of lysophosphatidic acid receptor 1 in inflammatory response induced by lipopolysaccharide from Porphyromonas gingivalis in human periodontal ligament stem cells

  • Kim, Dong Hee;Seo, Eun Jin;Tigyi, Gabor J.;Lee, Byung Ju;Jang, Il Ho
    • International Journal of Oral Biology
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    • 제45권2호
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    • pp.42-50
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    • 2020
  • Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.

Gintonin stimulates autophagic flux in primary cortical astrocytes

  • Rahman, Md. Ataur;Hwang, Hongik;Nah, Seung-Yeol;Rhim, Hyewhon
    • Journal of Ginseng Research
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    • 제44권1호
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    • pp.67-78
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    • 2020
  • Background: Gintonin (GT), a novel ginseng-derived exogenous ligand of lysophosphatidic acid (LPA) receptors, has been shown to induce cell proliferation and migration in the hippocampus, regulate calcium-dependent ion channels in the astrocytes, and reduce β-amyloid plaque in the brain. However, whether GT influences autophagy in cortical astrocytes is not yet investigated. Methods: We examined the effect of GT on autophagy in primary cortical astrocytes using immunoblot and immunocytochemistry assays. Suppression of specific proteins was performed via siRNA. LC3 puncta was determined using confocal microscopy. Results: GT strongly upregulated autophagy marker LC3 by a concentration- as well as time-dependent manner via G protein-coupled LPA receptors. GT-induced autophagy was further confirmed by the formation of LC3 puncta. Interestingly, on pretreatment with an mammalian target of rapamycin (mTOR) inhibitor, rapamycin, GT further enhanced LC3-II and LC3 puncta expression. However, GT-induced autophagy was significantly attenuated by inhibition of autophagy by 3-methyladenine and knockdown Beclin-1, Atg5, and Atg7 gene expression. Importantly, when pretreated with a lysosomotropic agent, E-64d/peps A or bafilomycin A1, GT significantly increased the levels of LC3-II along with the formation of LC3 puncta. In addition, GT treatment enhanced autophagic flux, which led to an increase in lysosome-associated membrane protein 1 and degradation of ubiquitinated p62/SQSTM1. Conclusion: GT induces autophagy via mTOR-mediated pathway and elevates autophagic flux. This study demonstrates that GT can be used as an autophagy-inducing agent in cortical astrocytes.

청소년의 스트레스 유형에 대한 프로파일 탐색 (A Study on the Profile Analysis of Types of Adolescents' Stress)

  • 임채영;염동문;정현태
    • 한국사회복지학
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    • 제68권2호
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    • pp.213-232
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    • 2016
  • 본 연구는 청소년들이 지각하는 스트레스 프로파일을 탐색하고, 프로파일에 나타난 집단별 특성변인의 영향을 알아보는데 목적이 있다. 한국청소년정책연구원의 '한국 아동 청소년 인권실태조사(2013)' 횡단자료를 이용하여 전국의 초등학교 4학년에서 고등학교 3학년에 재학 중인 9,521명의 청소년들을 대상으로 스트레스 유형에 대한 프로파일분석을 실시하였다. 분석 결과, 적합도 지수와 잠재계층 분류율에 따라 2개 계층 유형이 선택되었다. 1유형은 모두 낮은 수준으로 나타나 저위험집단으로, 2유형은 모두 높은 수준으로 나타나 상대적 위험집단으로 명명하였다. 청소년들의 스트레스 특성을 예측하기 위해 저위험집단을 기준으로 이항로지스틱회귀분석을 실시한 결과, 여학생이 남학생에 비해, 주관적 건강상태와 행복 정도가 낮을수록, 가출경험이 있을수록, 학업성적 수준과 가정의 경제적 사정이 낮을수록 상대적 위험집단에 속할 가능성이 높게 나타났다. 그러나 중학생은 가출경험과 학업성적수준에서, 고등학생은 학업성적수준에서 집단 간 차이가 유의미하지 않게 나타났다. 초등학생, 중학생, 고등학생, 전체 청소년에서 모두 저위험집단에 비해 상대적 위험집단에 속할 가능성에 가장 큰 영향을 미치는 것은 행복정도로 분석되었다. 본 연구의 시사점, 제한점, 후속연구의 방향을 제시하였다.

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Gintonin-mediated release of astrocytic vascular endothelial growth factor protects cortical astrocytes from hypoxia-induced cell damages

  • Choi, Sun-Hye;Kim, Hyeon-Joong;Cho, Hee-Jung;Park, Sang-Deuk;Lee, Na-Eun;Hwang, Sung-Hee;Rhim, Hyewon;Kim, Hyoung-Chun;Cho, Ik-Hyun;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • 제43권2호
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    • pp.305-311
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    • 2019
  • Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5- triphosphate receptor antagonist, 2-APB; and intracellular $Ca^{2+}$ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor-VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system.

효율적인 주파수 변조된 초음파 파형 발생을 위한 최적화된 시그마 델타 변조 기법 (Optimized Sigma-Delta Modulation Methodology for an Effective FM Waveform Generation in the Ultrasound System)

  • 김학현;한호산;송태경
    • 대한의용생체공학회:의공학회지
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    • 제28권3호
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    • pp.429-440
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    • 2007
  • A coded excitation has been studied to improve the performance for ultrasound imaging in term of SNR, imaging frame rate, contrast to tissue ratio, and so forth. However, it requires a complicated arbitrary waveform transmitter for each active channel that is typically composed of a multi-bit Digital-to-Analog Converter (DAC) and a linear power amplifier (LPA). Not only does the LPA increase the cost and size of a transmitter block, but it consumes much power, increasing the system complexity further and causing a heating-up problem. This paper proposes an optimized 1.5bit fourth order sigma-delta modulation technique applicable to design an efficient arbitrary waveform generator with greatly reduced power dissipation and hardware. The proposed SDM can provide a required SQNR with a low over-sampling ratio of 4. To this end, the loop coefficients are optimized to minimize the quantization noise power in signal band while maintaining system stability. In addition, the decision level for the 1.5 bit quantizer is optimized for a given input waveform, which results in the SQNR improvement of more than 5dB. Computer simulation results show that the SQNR of a FM(frequency modulated) signal generated by using the proposed method is about 26dB, and the peak side-lobe level (PSL) of its compressed waveform on receive is -48dB.

Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

  • Zhu, Yu;Liu, Xing-Jun;Yang, Ping;Zhao, Meng;Lv, Li-Xia;Zhang, Guo-Dong;Wang, Qin;Zhang, Ling
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3219-3226
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    • 2014
  • Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.