• Title/Summary/Keyword: ${\gamma}$-GTP

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The Signal Transduciton of Ginsenosides, Active Ingredients of Panax ginseng, in Xenopus oocyte: A Model System for Ginseng Study

  • Nah Seung-Yeol;Lee Sang-Mok
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.66-83
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    • 2002
  • Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

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The Clinical study in 60 cases for breast cancer patients on the effects by Hnagamdan(抗癌丹) (항암단(抗癌丹)을 투여한 유방암(乳房癌) 환자(患者) 60례(例)에 대한 임상보고(臨床報告))

  • Choi, Byung-Lyul;Lee, Yong-Yeon;Yoo, Hwa-Seung;Seo, Sang-Hoon;Choi, Woo-Jin;Cho, Jung-Hyo;Lee, Yeon-Weol;Son, Chang-Kyu;Cho, Chong-Kwan;Song, Kee-Cheol
    • The Journal of Internal Korean Medicine
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    • v.22 no.4
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    • pp.669-674
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    • 2001
  • Objectives: The purpose of this study was to examine the efficacy of Hangamdan(Kangaidan) on 60 patients who have suffered from breast cancer. Methods: Hangamdan(Kangaidan) was administered to patients for over 1 months continuously. We checked improvement of clinical symptoms, changes of chemistry hematological test. Results: The results obtained are summarized as follows. Hangamdan(Kangaidan) has significant effect on the improvement of clinical symptoms. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(92.1%) were observed. The effects of the symptoms were diarrhea(37.3%), abdominal pain (25.3%), general body weakness(22.9%), nausea(20.5%) and etc. in orders. And analysis of hematology attached by breast cancer, maintenance and increasing of WBC(89.9%), RBC(74.7%), Hgb(81.1%), Platelet(92.4%) were observed. After taken Hangamdan(Kangaidan), maintenance and decreasing of AST(85.9%), ALT(94.8%), ${\gamma}$-GTP(87.5%), BUN(88.3%), Creatinine(90.9%) were observed. And increasing of IL-12(25%), IFN-${\gamma}$(83%) were observed. Conclusions: From the above results, it is suggested that Hangamdan(Kangaidan) have significant effects on recovery of immune modulation.

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The Clinical study in 62 cases for lung cancer patients on the effects by Hangamdan(抗癌丹) (항암단(抗癌丹)을 투여(投與)한 폐암(肺癌) 환자(患者) 62례(例)에 대한 임상보고(臨床報告))

  • Choi, Byung-lyul;Son, Chang-kyu
    • Journal of Haehwa Medicine
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    • v.10 no.1
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    • pp.121-131
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    • 2001
  • Clinical studies were carried out 62 cases of patients with lung cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by lung cancer, by sex, showed that Male is more then Female, by age, showed that the number of sixties is majority. 2. Distribution of diagnostic stage, in descending order; stage IV(43.6%,top), stage III(35.5%), stage II(17.7%), stage I(3.2%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(84.0%) were observed. The effects of the symptoms were as follows; cough(50.0%), anorexia(48.4%), chest discomfort(31.0%), sputum(24.2%), general body weakness(11.3%), hemoptysis(9.7%) and etc. in orders. 4. Analysis of hematology attached by lung cancer, maintenance and increasing of WBC(98.4%), RBC(74.2%), Hgb(71.0%), Platelet(96.7%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(91.5%), ALT(93.2%), ${\gamma}-GTP$(95.0%), BUN(82.7%), Creatinine(93.3%) were observed. 5. Analysis of IL-12 and $IFN-{\gamma}$ attached by lung cancer, increasing of IL-12(31.3%), $IFN-{\gamma}$(72.7%) were observed. 6. Analysis of QOL attached by lung cancer, maintenance and improvement of combined treatment of western and oriental therapy(94.0%), traditional oriental therapy(91.7%) were observed. 7. Analysis of survival in patients with IV stage of lung cancer, above 7 months(22.2%), 12 months(70.4%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(50.0%) and maintenance and improvement of combined treatment of western and oriental therapy(80.0%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(50.0%), combined treatment of western and oriental therapy(60.0%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for lung cancer patients by combination with western therapy or alone.

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Hepatoprotective Effect of Grifola frondosa Water Extract on Carbon Tetrachloride-induced Liver Injury in Rats

  • Lee, Jong-Suk;Kim, Han-Sup;Lee, Yoon-Joo;Yong, Cheol-Soon;Choi, Han-Gon;Han, Gi-Dong;Kim, Jung-Ae;Lee, Jae-Sung
    • Food Science and Biotechnology
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    • v.17 no.1
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    • pp.203-207
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    • 2008
  • The present study aimed at assessing the protective effect of water extract from fruit body of the Grifola frondosa (GFW) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity. Rats orally administered with GFW 0.5, 1.0, 2.0 g/kg for 14 days were treated with $CCl_4$ to induce hepatotoxicity. Pretreatment with GFW remarkably prevented the elevation of serum AST, ALT, ALP, LDH, $\gamma$-GTP, and liver lipid peroxides in $CCl_4$-treated rat and GFW administration in liver injured rats by $CCl_4$ showed significant (p<0.05) protection of liver as evidenced from normal serum enzymes and malondialdehyde (MDA) levels. In the ultrastructural changes, administration of $CCl_4$-induced damage of hepatocytes with vacuolation, a highly damaged endoplasmic reticulum, and degenerating nuclei. However, pre-administration with GFW preserved normal ultrastructure of hepatocytes. These results suggest that GFW had an effect to inhibit $CCl_4$-induced liver injury in rat, and that it could be used as an effective hepatoprotective agent against chemical-induced liver damage.

A study on the renal dysfunction among workers exposed to organic solvent mixtures (저농도 복합유기용제 노출근로자의 신기능 변화에 관한 연구)

  • Kim, Jung Won;Paik, Soo Dong;Lee, Chang Hee;Kim, Jung Ho;Kang, Dong Mug;Moon, Deog Hwan;Lee, Chae Un
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.11 no.2
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    • pp.153-160
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    • 2001
  • Objectives : The authors evaluated the effects on renal function of workers chronically exposed to low-level organic solvent mixtures. Methods : The authors measured the level of urine ${\beta}2$-microglobulin(${\beta}2$-MG) and microalbumin as biochemical markers of renal function and damage in 29 male workers exposed to organic solvents for more than five years and compared their results with those of 30 male office clerks as a reference group. Results : 1. The mean values of hemoglobin, hematocrit, SGOT, SGPT, ${\gamma}$-GTP were all within normal limits and there was no significant difference, except for hemoglobin(p<0.01), between exposed and reference group. 2. The values of BUN and serum creatinine were within reference limits and there was no significant difference between exposed and reference group. 3. The difference of mean values of urine microalbumin corrected by urine creatinine were statistically significant (p<0.01), but those of urine ${\beta}2$-MG was not. 4. There were no correlation of urine hippuric acids with BUN, serum creatinine, urine microalbumin and ${\beta}2$-MG. 5. There were no significant difference of BUN, serum creatinine, urine microalbumin and ${\beta}2$-MG upon work duration. Conclusions: It is assumed that chronic low-level organic solvent exposure in these workers shows early renal dysfunction, glomerular changes. The result corresponds to previous studies showing the relationship between hydrocarbon exposure and glomerulonephritis. For evaluation of impairment on kidney tubules, we need further study using more precise markers and long-term follow-up.

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The Hematologic Study on Cerebral Infarction (뇌경색환자의 혈액학적 소견 연구)

  • Kim, Yoon-Sik
    • Journal of Haehwa Medicine
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    • v.12 no.2
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    • pp.1-9
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    • 2004
  • 1. Purpose Stroke is the most frequent cause of mortality and morbidity rate in Korea with coronary heart disease and cancer. The ischemic type of stroke is increasing tendency. The purpose of this studies is to examine the hematologic difference between cb infarction patients and Korean normal adults. 2. Method The study group consisted of neurologically confirmd 50 cb-infarction patients as the case group and 278 patients as control group that they had no significant result by CT through early examination of stroke in Cheonan oriental hospital of Daejeon university. We tested and compared RBC, hemoglobin, hematocrit, WBC, PT, PTT, total protein, albumin, total bilirubin, direct bilirubin, GOT GPT, $\gamma$-GTP, total cholesterol, triglyceride, HDL-C, glucose, BUN, creatinine, Na, K in the both group. 3. Result In the sample group(cb infarction group), there were many patients with low RBC count but no significant and with low hemoglobin, hematocrit(p<0.05). Thereas, increased WBC count and delayed PTT were showed respectively 20%, 36% in patient group, 7.9%, 4.7% in normal group(p<0.05). Comparing the LFT between cb infarction patients and normal adults, we founded significant cases with low HDL-C level, high glucose level, low potassium level in patient group(p<0.05). But the percentage of high total cholesterol level and triglyceride level were 18%, 29%(norma1 group), 20%, 28%(cb infarction group) respectively, there were no significant difference. 4. Conclusion In this study, we demonstrated that low HDL-C level and high glucose level is one of important risk factor of cb infarction. Also prospective studies are needed to evaluate many risk factor(hemoglobin, hematocrit, WBC, cholesterol, triglyceride, K, etc) of cb infarction.

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A Clinical Study on the Effect of Acupuncture Treatment for the Change of Milk Production (침치료가 산모의 모유량 변화에 미치는 영향에 대한 임상연구)

  • Kim, Tae-Hee;Park, Jeong-Kyoung;Song, Yun-Hui;Lee, Eun-Hee;Song, Beom-Yong;Yook, Tae-Han;Kim, Lak-Hyung
    • The Journal of Korean Obstetrics and Gynecology
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    • v.20 no.4
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    • pp.74-86
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    • 2007
  • Purpose: The aim of this study was to investigate the effect of Acupuncture Treatment on the change of milk production. Methods: The subjects were 43 women who admitted for postpartum treatment in Hospital of Woosuk University from 25th July 2005 to 25th May 2007. The Control group were 22 women and Acupunture treatment group were 21 women. In control group we measured only the breast milk amount and in acupunture treatment group we measured the breast milk amount after acupunture at Sot#aek(SI1), $Ch{\bar{o}}njung$(CV17), $Yug{\bar{u}}n$(ST18), Chok-Samni(ST36). We checked breast milk amount, VAS(satisfaction of breast milk amount), vital sign, wrong response everyday. We tested CBC, LFT(AST, ALT, ${\gamma}-GTP$), prolactin before and after clinical study. Results: VAS of acupunture treatment group was significantly decresed compared with that of control group. Conclusion: The results suggest that acupuncture treatment may be useful for breast feeding.

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$K^{+}$ 통로 개방제의 혈관근 이완작용에 대한 연구 : sarcoplasmic Reticulum에서의 $Ca^{++}$ 유리에 대한 효과

  • 임병용;홍선화;홍기환
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.288-288
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    • 1994
  • 1.목적 $K^{+}$ 통로 개방제인 cromakalim과 levcromakalim이 원형질막의 $K^{+}$ 통로를 개방시켜 막의 과분극을 일으킴으로서 강력한 혈관 이완작용을 일으킨다는 것은 주지하는 바다. 본 연구진들은 지난 2년간의 신약개발 연구사업을 통하여 cromakalim과 pinacidil 등 여러종의 K+통로개방제가 건전한 평활근 세포에서 phenylephrine뿐만 아니라 saponin처리에 의한 투과성 근세포 (permeabilized cells)에서 inositol 1,4,5-triphosphate (IP$_3$)에 의한 수축도 억제함을 보고 하였다. 본 연구에서는 이러한 수축작용에 대한 SPEX fluolog-2 spectrophotometer를 사용하여 돼지의 관상동맥 혈관근의 세포질내 $Ca^{++}$의 농도 ([$Ca^{++}$])의 변동을 관찰하였다. 정상 관상동맥 혈관근 조직에서 acetylcholine (0.1-1$\mu$M)에 의한 [Ca$^{++}$]농도의 증가와 b-escin 처리에 의한 skinned strip에서의 IP3 (1-5$\mu$M)에 의한 [Ca$^{2+}$]의 증가는 cromakalim과 levcromakalim의 전처치에 의하여 현저히 억제되었다. Skinned strip에서 이러한 K+ 통로 개방제에 의한 $IP_3$-요도 ($Ca^{2+}$)i 증가의 억제가 apamin (1-5 mM)과 glibenclamide (1$\mu$M)에 의하여 봉쇄되었으나, chrybdotoxin (0.1$\mu$M)에 의하여는 영향을 받지 아니하였다 한편 skinned strip에서 cromakalim은 GTP${\gamma}$s에 의한 [$Ca^{2+}$]i의 증가는 봉쇄하였으나 caffeine에 의한 [$Ca^{2+}$]i의 증가는 영향을 미치지 아니하였다. 이러한 연구결과로 보아 cromakalim과 levcromakalim과 같은 $K^{+}$ 통로 개방제가 세포막의 $K^{+}$ 통로를 개방하는 작용 뿐만 아니라 적어도 sarcoplasmic membrane에서 $Ca^{2+}$의 유리를 봉쇄함으로써 강력한 혈관 평활근 이완 작용을 나타내는 것으로 시사된다.

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The Effects of Lygodium japonicum on Experimental Rat Model of Benign Prostatic Hyperplasia (해김사(海金沙)가 Rat의 전립선비대에 미치는 영향)

  • Lee, Doo-Hyun;Lee, Jang-Sik;Kim, Young-Seung
    • The Journal of Internal Korean Medicine
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    • v.31 no.3
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    • pp.457-466
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    • 2010
  • Objective : In benign prostatic hyperplasia, dihydrotestosterone acts as a potent cellular androgen and promotes prostate growth. Inhibiting enzyme $5{\alpha}$-reductase that is involved in the conversion of testosterone to the active form dihydrotestosterone reduces this excessive prostate growth. The mechanism on benign prostatic hyperplasia is substantiating evidence to support the clinical value in the evaluation of therapeutic efficacy. In this study, we investigated the effects of Lygodium japonicum on cyto-pathological alterations and expression of $5{\alpha}$-reductase in the rat model of benign prostatic hyperplasia induced by castration and testosterone treatment. Methods : Sprague-Dawley rats were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Lygodium japonicum as an experimental specimen, and finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes and testosterone levels. Also, the prostates were observed by hematological alterations of AST, ALT, ${\gamma}$-GTP, BUN and creatinine. Results : The rats treated with Lygodium japonicum showed a diminished range of luminal cell and duct epithelial cell damage. The stromal elements and connective tissue proliferation of Lygodium japonicum treated group as compared to the control group decreased. Conclusions : These findings suggest that Lygodium japonicum may protect the glandular epithelial cells. We concluded that Lygodium japonicum could be a useful remedy agent for treating the benign prostatic hyperplasia.

Phospholipase D in Guinea Pig Lung Tissue Membrane is Regulated by Cytosolic ARF Proteins

  • Chung, Yean-Jun;Jeong, Jin-Rak;Lee, Byung-Chul;Kim, Ji-Young;Park, Young-In;Ro, Jai-Youl
    • Journal of Microbiology and Biotechnology
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    • v.13 no.6
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    • pp.897-905
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    • 2003
  • Phospholipase D (PLD) and ADP-ribosylation factor (ARF) were partially purified on a series of column chromatography, and their biochemical properties were characterized to understand the regulatory mechanism of PLD activation by ARF protein in the antigen-induced immune responses in guinea pigs. Heparin Sepharose and high-Q Sepharose column chromatographies were used for the purification of PLD, and Sephadex G-25, DEAE Sephacel, Source 15 PHE (HIC), Superdex-75, and Uno-Q column chromatographies were used for the purification of ARF. The purified PLD and ARF proteins were identified with anti-rabbit PLD- or ARF-specific antibodies, showing about 64 or 85 kDa for the molecular mass of PLD and 29 or 35 kDa for the sizes of ARF. Partial cDNA of ARF3 was cloned by RT-PCR in guinea pig lung tissue and its nucleotides and amino acids were sequenced. Guinea pig ARF3 showed 92% of nucleotides sequence identity and 100% of amino acid sequence homology with human ARF3. The ARF-regulated PLD activity was measured in the oleate or ARFs-containing mixed lipid vesicles. The purified and recombinant ARF (rARF) activities were assessed with the $GTP{\gamma}S$ binding assay. The PLD activity was induced by oleate in a dose-dependent manner. The purified ARF and recombinant ARF3 increased PLD activity in guinea pig lung tissues. These data show that the activity of membrane-bound PLD can be regulated by the cytosolic ARF proteins, suggesting that ARF proteins in guinea pig lung can act as a regulatory factor in controlling the PLD activity in allergic reaction.