Cyclobuxine D의 prostaglandin 합성과 백혈구 유주에 미치는 영향

이종화(Jong-Hwoa Lee),박영현(Young-Hyun Park),조병헌(Byung-Heon Cho),김유재(Yu-Jae Kim),김종배(Jong-Bae Kim),김정목(Chung-Mok Kim),김천숙(Chun-Sook Kim),차영덕(Young-Deog Cha),김영석(Young-Suk Kim) 대한약리학회 1987 대한약리학잡지 Vol.23 No.1

본 실험실에서는 회양목(Buxus microphylla var. koreana Nakai)으로 부터 steroid성 alkaloid인 cyclobuxine D를 분리하였고, 그의 여러 약리작용을 검색하고 있다. 본 연구에서는 cyclobuxine D의 guinea pig lung homogenate에서 prostaglandins의 합성에 미치는 영향과 carrageenin으로 유도한 염증에서 prostaglandin의 합성과 백혈구 유주에 대한 영향을 관찰하였다. Cyclobuxine D (up to 100ug/ml)는 guinea pig lung homogenate에 의한 prostaglandins 합성에 대해서는 현저한 영향이 없었으나, 20mg/kg에서 carrageenin으로 유도된 염증에서 prostaglandin의 합성과 백혈구 유주에 대해 현저한 억제작용을 나타낸다. Aspirin은 vivo와 vitro에서 prostaglandin의 합성을 억제하나, 염증 삼출물에서 백혈구 유주에 대해서는 영향이 거의 없다. Dexamethasone은 vitro에서 외인성 arachidcnic acid를 기질로 가했을때는 prostaglandin 합성에 대해 영향이 없었고 carrageenin으로 유도된 염증에서 prostaglandin의 합성과 백혈구 유주를 억제하였다. 이상의 결과로 cyclobuxine D의 항염증작용은 phospholipase A₂ activity를 저해하여 항염증 작용을 나타내는 것으로 사료되는 corticosteroid와 유사한 것으로 추정된다. Cyclobuxine D was extracted from Buxus microphylla var. koreana Nakai. The effects of cyclobuxine D on the biosynthesis of prostaglandins from arachidonic acid in guinea pig lung, prostaglandin production and leukocyte migration in carrageenin-induced inflammation was investigated. These effects of cyclobuxine D were compared with those of aspirin and dexamethasone. Cyclobuxine D does not inhibit significantly cyclooxygenase in guinea pig lung but reduces prostaglandin concentration and leukocyte migration in inflammatory exudates. These effects of cyclobuxine D differ from that of aspirin which inhibits biosynthesis of prostaglandin in vitro and has a relative small effect on leukocyte migration. Dexamethasone, which does not inhibit cyclooxygenase in vitro, has an effect similar to that of cyclobuxine D on leukocyte migration and prostaglandin production in inflammatory exudates.

Effects of Cyclobuxine D on the Biosynthesis of Prostaglandins in Vitro, Prostaglandins Production and Leukocyte Migration in Vivo

이종화,박영현,조병헌,김유재,김종배,김정목,김천숙,차영덕,김영석,Lee, Jong-Hwoa,Park, Young-Hyun,Cho, Byung-Heon,Kim, Yu-Jae,Kim, Jong-Bae,Kim, Chung-Mok,Kim, Chun-Sook,Cha, Young-Deog,Kim, Young-Suk The Korean Society of Pharmacology 1987 대한약리학잡지 Vol.23 No.1

Cyclobuxine D was extracted from Buxus microphylla var. koreana Nakai. The effects of cyclobuxine D on the biosynthesis of prostaglandins from arachidonic acid in guinea pig lung, prostaglandin production and leukocyte migration in carrageenin-induced inflammation was investigated. These effects of cyclobuxine D were compared with those of aspirin and dexamethasone. Cyclobuxine D does not inhibit significantly cyclooxygenase in guinea pig lung but reduces prostaglandin concentration and leukocyte migration in inflammatory exudates. These effects of cyclobuxine D differ from that of aspirin which inhibits biosynthesis of prostaglandin in vitro and has a relative small effect on leukocyte migration. Dexamethasone, which does not inhibit cyclooxygenase in vitro, has an effect similar to that of cyclobuxine D on leukocyte migration and prostaglandin production in inflammatory exudates. 본 실험실에서는 회양목(Buxus microphylla var. koreana Nakai)으로 부터 steroid성 alkaloid인 cyclobuxine D를 분리하였고, 그의 여러 약리작용을 검색하고 있다. 본 연구에서는 cyclobuxine D의 guinea pig lung homogenate에서 prostaglandins의 합성에 미치는 영향과 carrageenin으로 유도한 염증에서 prostaglandin의 합성과 백혈구 유주에 대한 영향을 관찰하였다. Cyclobuxine D (up to 100ug/ml)는 guinea pig lung homogenate에 의한 prostaglandins 합성에 대해서는 현저한 영향이 없었으나, 20mg/kg에서 carrageenin으로 유도된 염증에서 prostaglandin의 합성과 백혈구 유주에 대해 현저한 억제작용을 나타낸다. Aspirin은 vivo와 vitro에서 prostaglandin의 합성을 억제하나, 염증 삼출물에서 백혈구 유주에 대해서는 영향이 거의 없다. Dexamethasone은 vitro에서 외인성 arachidcnic acid를 기질로 가했을때는 prostaglandin 합성에 대해 영향이 없었고 carrageenin으로 유도된 염증에서 prostaglandin의 합성과 백혈구 유주를 억제하였다. 이상의 결과로 cyclobuxine D의 항염증작용은 phospholipase $A_2$ activity를 저해하여 항염증 작용을 나타내는 것으로 사료되는 corticosteroid와 유사한 것으로 추정된다.

Effects of Trithioformaldehyde on the Biosynthesis of Prostaglandin in Vitro, Prostaglandin Production and Leukocyte Migration in Vivo

Kim, Yu-Jae,Park, Young-Hyun,Kim, Jong-Bae,Kim, Chung-Mok,Cha, Young-Deog,Kim, Young-Suk,Cho, Byung-Heon,Kim, Chun-Sook,Lee, Jong-Hwoa 순천향대학교 1987 논문집 Vol.10 No.2

본 실험실에서는 trithioformaldehyde (TTFA)를 합성하여, TTFA의 여러 약리작용을 검색하고 있다. 본 연구에서는 TTFA의 guinea pig lung homogenate에서 prostaglandins의 합성에 미치는 영향과 carrageenin으로 유도된 염증 산출물에서 prostaglandin의 생성과 백혈구 유주에 대한 작용을 관찰하였다. TTFA(up to 1000㎍/ml)는 guinea pig lung homogenate에 의한 prostaglandin의 합성을 유의하게 억제하였으며, 20㎎/㎏에서 carrageenin으로 유도된 염증에서도 prostaglandin의 생성을 53% 정도 억제하였다. 그러나 백혈구 유주는 TTFA에 의해 약간 증가되었다. Aspirin은 vivo에서 prostaglandin의 합성을 억제하나, 염증 삼출물에서 백혈구 유주에 대해서는 거의 영향이 없었다. Dexamethasone은 vitro에서 외인성 arachidonic acid를 기질로 가했을 때는 prostaglandin 합성에 영향이 없었고 carrageenin으로 유도된 염증에서는 prostaglandin의 생성과 백혈구 유주를 억제하였다. 이상의 결과로 trithioformaldehyde(TTFA)는 항염증 작용을 나타내며 이 작용은 cyclooxygenase를 억제하여 항염증 작용을 나타내는 aspirin 유사약물과 유사한 것으로 추정된다. Trithioformaldehyde(TTFA) was synthesized from formalin and hydrogen sulfide in our Lab. The effects of TTFA on the biosynthesis of prostaglandins from arachidonic acid in guinea pig lung, prostaglandin production and leukocyte migration in carrageenin-induced inflammation were investigated. These effects of TTFA were compared with those of aspirin and dexamethasone. TTFA inhibited cyclooxygenase in guinea pig lung homogenate and reduced rostaglandin concentration in inflammatory exudates. TTFA increased slightly leukocyte migration in inflammatory exudates. These effects of TTFA were similar to that of aspirin which inhibited biosynthesis of prostaglandin in vitro and had a relative small effect of leukocyte migration. Dexamethasone, which did not inhibit cyclooxygenase in vitro, had an effect different from that of TTFA on leukocyte migration in inflammatory exudates.

Effects of Prostaglandins on Embryonic Expansion and Hatching by Developmental Stage in Mouse

전용필,김정훈,윤용달,김문규 한국발생생물학회 1998 발생과 생식 Vol.2 No.2

The effects of prostaglandins in hatching and implantation have been studied but the results were various, and those are not well known by the embryonic stage. The present study examined the effects of prostaglandin (PG ) and prostaglandin (PG ) on the expansion and hatching of mouse embryos by embryonic stage. Also we tried to measure the concentration of prostaglandins of morula, expanded, and hatching embryos. In early morula stage embryos, high concentration of PG (>100 μM) showed cytotoxicity but PG did not. The hatching was inhibited all groups but not gave negative effects on expansion. In 84 hr and 96 hr stage embryos, the hatching rate was decreased at all treatment groups but not inhibited the expansion. When combine prostaglandin with indomethacin, the hatching rate was increased significantly compared to the prostaglandin-treated groups, and as lower and lower the PG concentration, the hatching rate increased to the control level. The embryonic synthesis of PG increased dramatically but that of PG increased gradually. PG showed cytotoxicity at early stage embryos much than late stage embryos, but PG did not. Hatching was inhibited by the high PG concentration. It is suggested that the inhibition of hatching might be at resulted from cytotoxicity of PG on embryo. However, it is thought that the mechanisms of inhibition of hatching are different between PG and PG . In conclusion, it can be suggested that PG and PG concerned with the expansion and hatching, and their effects on hatching were different by the embryonic stage.

요관압 상승시 신혈류량 조절에 prostaglandin이 미치는 효과

민영기,양훈모,김종규,이석호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Higher ureteral pressure than in normal condition causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Higher ureteral pressure increased renal prostaglandin production, it is not clear whether or not it is also responsible for partial impairment of the autoregulation of RBF. Therefore, we investigated the role which prostaglandin play in the autoregulation of RBF, studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. For the purpose of this experiment, six anesthetized mongrel dogs were prepared for the measurements of RBF, mean systemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure to 0 cmH20, 20 cmH20 and 40 cmH20. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 20 cm and 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from 167±11 ml/min to 185±8 ml/min, 204±11 ml/min respectively and the renal arterial pressure and the systemic arterial pressure didn't change significantly. During 0 mmHg of ureteral presure threshold pressure of RBF autoregulation was 59±3 mmHg. On the other hand, during 20 cmH20, 40 cmH20 of ureteral pressure, the autoregulation curves shifted upward and rightward from control, threshold pressure is elevated by 74±3 mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulation during both control (63±5 mmHg) and the elevated ureteral pressure (77±5 mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin by increased ureteral pressure or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatore capacity during elevated ureteral pressure. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at 0 mmHg of ureteral pressure and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.

Mycobacterium Tuberculosis에 감염된 사람의 단구 유래 대식세포에서 신호전달 및 기능

김태전,김세곤 凡石學術奬學財團 2000 凡石學術論文集 Vol.4 No.1

Mycobacterium tuberculosis provided by Tuberculosis Research Institute was used to induce macrophage by using interferon-γ(IFN-γ) and lipopolysaccharide to monocyte from human peripheral blood. Four groups consisted of macrophage phagocyted by alive M. tuberculosis. macrophage phagocyted with killed M. tuberculosis. macrophage phagocyted with microbead. and macrophage without phagocyted(Figure 1-A, 1-B). Prostaglandin products. H_(2)O_(2) products. and intracellular calcium ion were measured by radioimmunoassay method. Cytofluor^(2300) fluorometer method. and confocal microscopy. The viability of M. tuberculosis phygocyted was measured by reverse transcriptase(RT)-PCR to investigate produced protein difference during the phagocytosis. Finally. two-dimensional gel electrophoresis method was used to identify produced intracellular protein difference. The results were summarized as follows. 1. There was a statistically significant differences in the amount of produced Prostaglandin among four groups(P<0.01). The amounts of produced prostaglandin by macrophage phagocyted with microbead and killed M. tuberculosis were 1.5 and 3.0 times higher than that of control group(173.23±23.45pg/ml) respectively. The amount of produced prostaglandin by macrophage phagocyted with alive M. tuberculosis was significantly higher than that of control group specially(P<0.0l). The amount of thromboxan B_(2)(TXB_(2)) and 6-keto-F1α by macrophage phagocyted with alive M. Tuberculosis were 1.9 and 2.7 times higher than that of control group respectively. However. the increased amounts were not as high as the increased amounts of Prostaglandin E_(2)(PGE_(2))(Table 2). 2. Table 3 shows macrophages and H_(2)O_(2) products by macrophages. The amount of H_(2)O_(2) produced were 1.4 to 3.1 times higher than that of negative control group(1.023±l05 C.F.U). The amount of produced H_(2)O_(2) in positive control group and experimental groups after treated with Phobol myristate acetate (PMA) was 4.3 to 5.2 times higher than that of negative control group. The amount of produced H_(2)O_(2) treated with PGE_(2) was lower than that of negative control group and the amounts of produced H_(2)O_(2) after treated with IFN-γ and interleukin (IL-2) were higher than that of negative control group. The amount of H_(2)O_(2) by macrophage phagocyted with alive M. tuberculosis showed the highest value regardless of stimulation reagents. There were statistically significant differences in the amount of produced H_(2)O_(2) between the control group and the experimental group with alive M. tuberculosis treated with PGE₂and IFN-γ especially(P<0.01)(Table 3). 3. The effect of prostaglandin increased with M. tuberculosis infection on intercellular calcium ion release was investigated. The amount of release was highest in macrophage phagocyted with alive M. tuberculosis followed by macrophage phagocyted with killed M. tuberculosis and macrophage phagocyted with microbead (Figure 2). 4. The result of viability of M. tuberculosis by RT-PCR showed that M. tuberculosis was able to survive three days (Figure 3-B). The result also showed that it was possible to identify the DNA upto six days after the culture regardless of M. tuberculosis survival(Figure 3-A). 5. The produced protein differences among the experimental groups was investigated using M tuberculosis infection in the second day of the viability decided by RT-PCR. The result showed that there was a protein found in groups phagocyted with killed and alive M. tuberculosis which was not found in microbead. The test result also indicated that there was a produced protein differences among the experimental groups and there was a protein that was specifically increased in alive M. tuberculosis groups(Figure 4-A.B.C).

Prostaglandin系와 Kinin-kallikrein系

진홍용 중앙대부설한국의과학연구소 1991 한국의과학 Vol.23 No.4

하부요로증상이 있는 남성 환자에서 요내 Prostaglandin의 변화

차승훈,김준철,박은영,서성일,박용현,황태곤 대한배뇨장애 및 요실금학회 2003 International Neurourology Journal Vol.7 No.2

Effect of Prostaglandins D<SUB>2</SUB>, E<SUB>2</SUB> and I<SUB>2</SUB> on the Regulation of K<SUB>ATP</SUB> Channel Activity in Rat Cardiac Myocytes

Jeong-Min Ju,Seung-Yeol Nah,Jae-Ha Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.5

<P> Contribution of prostaglandins D<SUB>2</SUB>, E<SUB>2</SUB> and I<SUB>2</SUB> (PGD<SUB>2, </SUB>PGE<SUB>2 </SUB>and PGI<SUB>2</SUB>) on the regulation of ATP-sensitive K<SUP>⁢</SUP> channel (K<SUB>ATP </SUB>channel) was investigated in isolated single rat ventricular cardiac myocytes using the patch clamp technique. PGD<SUB>2</SUB>, PGE<SUB>2</SUB> and PGI<SUB>2</SUB> did not affect K<SUB>ATP</SUB> channel activity in the inside-out patch, but increased channel activity in a dose-dependent manner when the channel activities were attenuated by the administration of 100 μM ATP to the internal solution in the inside-out patch. Channel activations by the prostaglandins were abolished by 50 μM glibenclamide, a K<SUB>ATP</SUB> channel blocker. Dose-response curves of relative channel activity against the ATP concentrations of internal solution in the inside-out patch were shifted to the right in the presence of those three prostaglandins. The rank order of the channel stimulatory potencies (as IC<SUB>50</SUB> for ATP) calculated from the dose-response curves were PGI<SUB>2</SUB> > PGD<SUB>2</SUB> > PGE<SUB>2</SUB>. Conductance of the channel was not changed by those three prostaglandins. In conclusion, we suggest that prostaglandins D<SUB>2</SUB>, E<SUB>2</SUB> and I<SUB>2</SUB> are involved in the regulation of K<SUB>ATP </SUB>channel activity in certain circumstances, and that those three prostaglandins may cause myocardial relaxation by opening K<SUB>ATP</SUB> channels, thus protecting the heart from ischema.

대장암에서 Prostaglandin의 역할

명승재 ( Seung Jae Myung ),김인화 ( In Hwa Kim ) 대한소화기학회 2008 대한소화기학회지 Vol.51 No.5

Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression. (Korean J Gastroenterol 2008;51:274-279)