• Title/Summary/Keyword: $AT_{1}$receptor

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Study on The Preventive Effect of Ginsenosides Against Hypercholesterolemia and Its Mechasnism (인삼사포닌의 고 cholesterol 혈증 강하작용에 관한 연구)

  • 윤수희;주충노
    • Journal of Ginseng Research
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    • v.17 no.1
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    • pp.1-12
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    • 1993
  • The Preventive effect of the saponin fraction of Panax ginseng C.A. Meyer against hyperchole- sterolemia was demonstrated by assaying the cholesterol and triacylglyceride level of the blood serum and liver of rats fed high-cholesterol diet with and/or without ginsenoside. To understand the mechanism of the preventive action of ginsenoside, ginsenoside effect on LDL receptor binding ability, cholesterol level, and cAMP level of Chinese hamster ovary (CHO) cells cultured under various conditions were examined. When LDL (20 $\mu$g/ml) was added to the culture medium for CHO cell culture, LDL receptor binding activity of the cell was suppressed down to 58% of that of normal group. Ginsenosides at 10--2% and 10-3% level (w/v) were shown to exert an appreciable stimulatory effect on CHO cell LDL receptor activity, which partially overcame the suppression due to the presence of LDL (20 $\mu\textrm{g}$/ml) in the medium. Ginsenosides also reduced the increased cholesterol level of test group almost to that of normal group, and it increased cAMP level, which was usually reduced to 55% of that of the normal group due to the presence of LDL in the medium. Comparison of Kd and Bmax value of CHO cells cultured under different conditions revealed that this stimulation was due not to the receptor's binding affinity but to its number. Addition of ginsenoside (10-2%) decreased the uptake of taurocholic acid as much as 20% at the actively transporting everted ileal sacs, but it failed to form a large mixed micelles with taurocholic acid, which was one of the proposed mechanisms by which ginsenoside inhibits bile acid reabsorption. From the above results, it seemed likely that ginsenoside prevented hypercholestrolemia by decreasing cholesterol level in cells thereby relieving the inhibition of LDL receptor synthesis by cholesterol and also by inhibiting bile acid reabsorption from the small intestine.

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Effects of Glutamate Receptor Antagonists and Protein Synthesis Inhibitor on Delayed Neuronal Death Induced by Transient Global Ischemia in Rat Brain

  • Ko, Jun-Seog;Bae, Choon-Sang;Kim, Jong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.3
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    • pp.279-286
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    • 1998
  • It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

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The Role of Opioid Receptor on the Analgesic Action of Intrathecal Sildenafil in Rats (백서의 척수강 내로 투여한 Sildenafil의 진통효과에 대한 Opioid 수용체 역할에 관한 연구)

  • Lee, Hyung Gon;Jeong, Chang Young;Yoon, Myung Ha;Kim, Woong Mo;Shin, Seung Heon;Kim, Yeo Ok;Huang, Lan Ji;Cui, Jin Hua
    • The Korean Journal of Pain
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    • v.20 no.1
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    • pp.21-25
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    • 2007
  • Background: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. Methods: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. Results: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. Conclusions: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.

The Effects of Nerve Growth Factor Expression of Central Nerve System by Environmental Enrichment and Peripheral Nerve Electrical Stimulation in Brain Ischemia Model Rats (뇌졸중 유발 백서모델에서 환경강화와 말초신경전기자극이 중추신경계의 신경성장인자에 미치는 영향)

  • Kim, Sa-Youl;Kim, Eun-Jung;Kim, Gye-Yeop
    • The Journal of Korean Physical Therapy
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    • v.19 no.4
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    • pp.33-41
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    • 2007
  • Purpose: To investigate environmental enrichment and nerve stimulation follows in application times with the change of BDNF & Trk-B receptor in the motor cortex and spinal cord. Methods: Experimental groups were divided into the five groups. Group I: normal control group, Group II: experiment control group, Group III: sciatic never electrical stimulation after MCAO, Group IV: application of only environmental enrichment after MCAO, Group V: never electrical stimulation with environmental enrichment after MCAO. Histologic observation and coronal sections were processed individually in goat polyclonal antibody phosphorylated BDNF and rabbit polyclonal antibody Trk-B receptor. Results: In immunohistochemistric response of BDNF and Trk-B, group II were showed that lower response effect at postischemic 1 days, 3 days, and 7 days. Group V were showed that increase response effect at postischemic 3 days, 7 days and 14 days. Specially showed that the most response effect at postischemic 14 days. In neurobehavioral assessment, group V were significantly difference from other groups on between-subject effects. Conclusion: The above results suggest that combined environmental enrichment with peripheral nerve electrical stimulation in focal ischemic brain injury were more improved that the change of BDNF & Trk-B receptor expression than non treatment.

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TGF-beta1, and TGF-beta Receptor Type I and Type II are present in Bovine Embryos

  • Kim, B. K.;H. J. Chung;Park, J. H.;J. H. Woo;Park, M. Y.;H. H. Seong;W. K. Chang
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.69-69
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    • 2003
  • Although effect of TGF$\beta$$_1$ on preimplantation embryo development was reported at mice, little information relevant to this subject is known in bovine. The objectives of this study were to investigate TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors type I and II expression, known as important factors in the embryo development, at unfertilized oocytes and fertilized embryos that will be used as basic data to be compared to NT embryos. We postulated that TGF$\beta$$_1$ may have a beneficial effect on the preimplantation embryo and show different expression patterns as embryo stages change. We have used immunocytochemistry to investigate the presence in unfertilized oocytes and preimplantation embryos of TGF$\beta$$_1$ and the essential components of the TGF$\beta$$_1$ signalling pathway, TGF$\beta$$_1$ receptors type I and II. We found that both receptors, as well as TGF$\beta$$_1$, were present in the unfertilized oocytes. This indicates that TGF$\beta$$_1$, is a maternally expressed protein. At the morulae and blastocyst stages the TGF$\beta$$_1$ receptor type II was not present, but the TGF$\beta$$_1$ receptor type I was present at both stages and we can confirm the TGF$\beta$$_1$ expression of high level at 8-cell stage. These findings support our hypothesis that the TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors may interact with the oocyte and preimplantation embryo, and that TGF$\beta$$_1$ signalling may be important for the development of the oocyte and the preimplahtation embryo.

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The Expression Pattern of Melatonin Receptor 1a Gene during Early Life Stages in the Nile tilapia (Oreochromis niloticus)

  • Jin, Ye Hwa;Park, Jin Woo;Kim, Jung-Hyun;Kwon, Joon Yeong
    • Development and Reproduction
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    • v.17 no.1
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    • pp.45-53
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    • 2013
  • The action of melatonin within the body of animals is known to be mediated by melatonin receptors. Three different types of melatonin receptors have been identified so far in fish. However, which of these are specifically involved in puberty onset is not known in fish. We cloned and analyzed the sequence of melatonin receptor 1a (mel 1a) gene in Nile tilapia Oreochromis niloticus. In addition, we examined the tissue distribution of gene expressions for three types of receptors, mel 1a, 1b and lc and investigated which of them is involved in the onset of puberty by comparing their expression with that of gonadotropin-releasing hormone receptor I (GnRHr I) gene using quantitative real-time PCR from 1 week post hatch (wph) to 24 wph. The mel 1a gene of Nile tilapia consisted of two exons and one bulky intron between them. Mel 1a gene was found to be highly conserved gene showing high homology with the corresponding genes from different teleost. All three types of melatonin receptor genes were expressed in the brain, eyes and ovary in common. Expression of mel 1a gene was the most abundant and ubiquitous among 3 receptors in the brain, liver, gill, ovary, muscle, eye, heart, intestine, spleen and kidney. Mel 1b and mel 1c genes were, however, expressed in fewer tissues at low level. During the development post hatch, expressions of both mel 1a and GnRHr I genes significantly increased at 13 wph which was close to the putative timing of puberty onset in this species. These results suggest that among three types of receptors mel 1a is most likely associated with the action of melatonin in the onset of puberty in Nile tilapia.

Expression Patterns of $TGF-{\beta}1,\;TGF-{\beta}$ Receptor Type I, II and Substrate Proteins Smad 2, 3, 4 and 7 in Bovine Oocytes and Embryos

  • Chung, Hak-Jae;Kim, Bong-Ki;Kim, Jong-Mu;Lee, Hyun-Gi;Han, Joo-Hee;Kim, Nam-Hyung;Park, Jin-Ki;Seong, Hwan-Hoo;Yang, Boh-Suk;Chang, Won-Kyong;Ko, Yeoung-Gyu
    • Reproductive and Developmental Biology
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    • v.30 no.4
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    • pp.271-277
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    • 2006
  • Transforming growth $factor-{\beta}\;(TGF-{\beta})$ has been shown to have a positive effect on in vitro fertilization (IVF) and has been reported to stimulate meiosis at follicular level in variety of species. The study was designed to determine the expression patterns of $TGF-{\beta}1,\;TGF-{\beta}$ receptors type I, II and Smads gene in bovine oocytes and embryos. $TGF-{\beta}1$ and their receptors were observed in the unfertilized oocytes. $TGF-{\beta}1$ and type II receptor were not expressed at the blastocyst stage, however, only type I receptor was exclusively observed at the same stage. The blastocyst stage, in particular, showed high levels of mRNA expression patterns containing a $TGF-{\beta}1$ type I receptor. The mRNA expression pattern of Smad 2 at all stages of embryonic development was similar in all respect with $TGF-{\beta}1$ type I receptor. On the contrary, Smad 3 and 4 were expressed with high and low level mRNA at the blastocyst stage. In conclusion. it is suggested that $TGF-{\beta}1$ signaling may be regarded as an important entity during the preimplantation embryo development.

Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor

  • Cha, Seung Ah;Park, Byung Mun;Kim, Suhn Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.4
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    • pp.447-456
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    • 2018
  • Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.

Effects of $17{\beta}$-Estradiol and Estrogen Receptor Antagonists on the Proliferation of Gastric Cancer Cell Lines

  • Kim, Myung-Jin;Cho, Sung-Il;Lee, Kun-Ok;Han, Hyung-Joon;Song, Tae-Jin;Park, Seong-Heum
    • Journal of Gastric Cancer
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    • v.13 no.3
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    • pp.172-178
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    • 2013
  • Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

Identifications of Source Locations for Atmospheric Total Gaseous Mercury Using Hybrid Receptor Models (Hybrid receptor model을 이용한 대기 중 총 가스상 수은의 오염원 위치 추정 연구)

  • Lee, Yong-Mi;Yi, Seung-Muk;Heo, Jong-Bae;Hong, Ji-Hyoung;Lee, Suk-Jo;Yoo, Chul
    • Journal of Environmental Science International
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    • v.19 no.8
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    • pp.971-981
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    • 2010
  • The objectives of this study were to measure ambient total gaseous mercury (TGM) concentrations in Seoul, to analyze the characteristics of TGM concentration, and to identify of possible source areas for TGM using back-trajectory based hybrid receptor models like PSCF (Potential Source Contribution Function) and RTWC (Residence Time Weighted Concentration). Ambient TGM concentrations were measured at the roof of Graduate School of Public Health building in Seoul for a period of January to October 2004. Average TGM concentration was $3.43{\pm}1.17\;ng/m^3$. TGM had no notable pattern according to season and meteorological phenomena such as rainfall, Asian dust, relative humidity and so on. Hybrid receptor models incorporating backward trajectories including potential source contribution function (PSCF) and residence time weighted concentration (RTWC) were performed to identify source areas of TGM. Before hybrid receptor models were applied for TGM, we analysed sensitivities of starting height for HYSPLIT model and critical value for PSCF. According to result of sensitivity analysis, trajectories were calculated an arrival height of 1000 m was used at the receptor location and PSCF was applied using average concentration as criterion value for TGM. Using PSCF and RTWC, central and eastern Chinese industrial areas and the west coast of Korea were determined as important source areas. Statistical analysis between TGM and GEIA grided emission bolsters the evidence that these models could be effective tools to identify possible source area and source contribution.