• YAKHAK HOEJI
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• v.49 no.4
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• pp.260-267
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• 2005

[ $PGE_1$ ] is an endogenous substance of potent vasodialator as well as inhibitor of platelet aggregation. It has been used therapeutically in peripheral arterial occlusive disease and impotence. Intracavernous injection of $PGE_1$ for erectile dysfunction has been established for several years as a treatment option for erectile dysfunction of diverse etiologies, but this mode of administration is limited by penile discomfort, pain at the injection site, inconvenience and noncompliance. As the matter of worse, the $\beta-hydroxy$ moiety of $PGE_1$ is extremely susceptible to dehydration in solution to give inactive $PGA_1$ and $PGB_1$. For the improvement of stability, rapid absorption at action site and the convenience of application, $PGE_1$ was formulated as urethral suppositories of three types of formulations, such as PEG, witepsol, and the mixture of PEG and witepsol. The stability test of $PGE_1$ and the release test in urinary suppositories were performed. Futhermore, the effect of enhancers and vehicle composition on the penetration of $PGE_1$ through excised rat skin was evaluated by permeability coefficient and enhancement ratio.

• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1675-1681
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• 2019

Clostridium difficile toxin A is known to cause colonic epithelial cell apoptosis, which is considered the main causative event that triggers inflammatory responses in the colon, reflecting the concept that the essential role of epithelial cells in the colon is to form a physical barrier in the gut. We previously showed that toxin A-induced colonocyte apoptosis and subsequent inflammation were dependent on prostaglandin E2 ($PGE_2$) produced in response to toxin A stimulation. However, the molecular mechanism by which $PGE_2$ mediates cell apoptosis in toxin A-exposed colonocytes has remained unclear. Here, we sought to identify the signaling pathway involved in toxin A-induced, $PGE_2$-mediated colonocyte apoptosis. In non-transformed NCM460 human colonocytes, toxin A exposure strongly upregulated expression of Bak, which is known to form mitochondrial outer membrane pores, resulting in apoptosis. RT-PCR analyses revealed that this increase in Bak expression was attributable to toxin A-induced transcriptional upregulation. We also found that toxin A upregulation of Bak expression was dependent on $PGE_2$ production, and further showed that this effect was recapitulated by an Prostaglandin E2(PGE2) receptor-1 receptor agonist, but not by agonists of other EP receptors. Collectively, these results suggest that toxin A-induced cell apoptosis involves $PGE_2$-upregulation of Bak through the EP1 receptor.

• Korean Journal of Veterinary Research
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• v.48 no.1
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• pp.17-26
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• 2008

This study was carried out to evaluate the antitumor, hepatoprotective and antimutagenic activities on hot water extract of Phellinus gilvus (PGE). Growth of tumor in mice that were orally given $0.25,0.5,1.0,2.0g\;kg^{-1}$ dose of PGE was inhibited in a dose-dependent manner (p < 0.05). The hepatoprotective effect of PGE in the carbon tetrachloride ($CCl_4$)-intoxicated rats was studied. In $CCl_4$ + PGE group, PGE was orally administered with 100 mg/kg/day dose 7 days before the treatment of $CCl_4$. The serum activity of aspartate aminotransferase and alanine aminotransferase in $CCl_4$ + PGE group were decreased at a rate of 59.6% and 54.1% compared with those in $CCl_4$ group, respectively (p < 0.05). Also, total cholesterol and triglyceride in $CCl_4$ + PGE group were significantly decreased at a rate of 90% and 73.6% compared with those in $CCl_4$ group (p < 0.05). In the Ames test, we confirmed PGE doesn't have any activity as a mutant, and PGE showed inhibitory effect against mutagenesis induced by 2-amino fluride and sodium azide in Salmonella typhimurium TA98, TA100 and TA1535 in a dose-dependent manner. From the above results, we may suggest that PGE might have useful as a material for functional food and/or animal pharmaceutics.

• Toxicological Research
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• v.20 no.1
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• pp.37-42
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• 2004

This study was undertaken to investigate comparative anti-tumor activity of water extracts of Phellinus gilvus (PGE), Phellinus linteus (PLE), and Phellinus baumii (PBE) in vitro. The anti-tumor activity in the present study was evaluated by sulforhodamine B (SRB) and microtetrazolium (MTT) assay in terms of cell survival level. The tumor cells (sarcoma 180 and P388) were treated with PGE, PLE, and PBE (7.5, 15, and 30 $\mu\textrm{g}$/ml) and Doxorubicin (DOX) (0.001~10 $\mu\textrm{M}$). The results showed that DOX, PGE, and PLE inhibited proliferation showing a dose-dependent manner against both tumor cells. However, PBE was inhibited by the only 30 $\mu\textrm{g}$/ml in both cells proliferation. In conclusion, all of PGE, PLE, and PBE used in this study have shown anti-tumor activity against both sarcoma 180 and P388. Among them, PLE was the most effective in anti-tumor activity against sarcoma 180 (p<0.05) and PGE was against P388 in SRB assay. PLE, however, was against P388 (p<0.05) in MTT assay.

• Journal of Radiation Protection and Research
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• v.14 no.1
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• pp.8-15
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• 1989

After administration of $^{99m}TC,\;^{67}Ga,\;^{131}I,\;^{32}P\;and\;^{238}U(UO_2(NO_2)_3{\cdot}6H_2O)$, in male rats, toxic effects were examined by determining the biological materials in blood. Dosages of radio-nuclides injected are based on the amounts routinely administered to patients, and concentrations of BUN, creatinine, SGOT, SGPT and $PGE_2$ in plasma are determinated as indices to the biochemical response. No increase of creatinine was observed after injection of $^{99m}TC$. Concentrations of BUN, SGOT and $PGE_2$ were not significantly increased in comparison with before-administration. Administration of $^{67}Ga,\;^{131}I\;and\;^{32}P$, did not significantly change BUN, SGPT and SGOT, but largely increased $PGE_2$ than control levels. Besides, $^{238}U$ Showed the most severe toxicity. From the above results, we suggest that the determination of $PGE_2$ in plasma can be used as an index in case of elvaluating the effects of radiation toxicity by nuclides used in nuclear medicine.

• Journal of Life Science
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• v.20 no.6
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• pp.845-852
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• 2010

Our previous study showed that lungs infected by Pseudomonas, a gram-negative bacteria, produce prostaglandin $D_2$ ($PGD_2$) and prostaglandin $E_2$ ($PGE_2$), the two major prostanoids generated by cyclooxygenase-2 (COX-2), and that the ratio of $PGD_2$ and $PGE_2$ can affect the outcome of the bacterial lung infection. In this study, we sought to uncover the mechanism that determines the ratio of $PGD_2$ and $PGE_2$ produced in lung inflammation. When treated with lipopolysaccharide (LPS), primary alveolar macrophages, extracted from mouse lung, more $PGE_2$ was produced than $PGD_2$, whereas MH-S, a murine alveolar macrophage cell line, produced more $PGD_2$ than $PGE_2$ in a similar experiment. Western blot analyses showed that the kinetics of COX-2 expression in both cell types is similar and epigenetic silencing of COX-2 expression did not affect expressions of lipocalin-PGD synthase (L-PGDS) and PGE synthase (mPGES-1), major enzymes synthesizing $PGD_2$ and $PGE_2$ in inflammation, respectively, indicating no effect of COX-2 on expressions of the two enzymes. Expressions of L-PGDS and mPGES-1 were also similar in both cell types, suggesting no effect of the two key enzymes in determining the ratio of $PGD_2$ and $PGE_2$ in these cells. A single intraperitoneal injection of LPS to C57BL/6 mice induced COX-2 expression and, similar to alveolar macrophages, produced more $PGE_2$ than $PGD_2$ in the lung. These results suggest that the differential expressions of $PGD_2$ and $PGE_2$ in the lung reflect those in alveolar macrophages and may not be directly determined by the enzymes responsible for $PGD_2$ and $PGE_2$ synthesis.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• Development and Reproduction
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• v.12 no.3
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• pp.267-274
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• 2008

Differentiation of blastocyst is critical step for implantation and is under the control of regulation factors originated from embryo or reproductive tracts. The sequential communication with those factors is suspected as critical events for differentiation. It has been suggested that intracellular signaling pathways activated by calcium is essential in differentiation of blastocyst. Previously, it was known that concanavalin A (Con A) increase the levels of free calcium in blastocyst stage. However, Con A can not accelerate the hatching, although heparin-binding epidermal growth factor-like growth factor (HB-EGF), a modulator of calcium level, accelerate the hatching of blastocyst. In this study, it was investigated whether Con A or prostaglandin $E_2$ ($PGE_2$) can modulate the differentiation of blastocyst. Con A accelerated the expansion of blastocyst in both 1 hr pulse treatment group and continuous treatment group. However, Con A significantly suppressed the hatching in both groups. The inhibition was significantly strong in continuous treatment group compared with 1 hr pulse treatment group. On the other hand, $PGE_2$ induced the increase the free calcium level, but did not accelerate the expansion. In addition $10{\mu}m\;PGE_2$ inhibited hatching. However, $PGE_2$ could accelerate hatching in Con A pretreated blastocyst. $PGE_2$ also caused the increase of free calcium level in Con A pretreated blastocyst. From these results, it is suggested that changes of the free calcium level induce a different calcium-mediated signaling pathways. In addition, sequential stimulation by signal molecules may triggers the cellular mechanisms for the differentiation of blastocyst.

• The Korean Journal of Zoology
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• v.30 no.4
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• pp.341-350
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• 1987

LHRH분비와 환denylate cyclase활성에 미치는 PGE2, Opioid, 그리고 Ca2+의 영향을 흰쥐의 시상하부 조직을 사용하여 조사하였다. K+(30mM)에 의한 LHR광분비촉진은 Ca2+의존적인데 반하여, PGE2에 의해 촉진되는 LHR노 분비는 세포의 Ca2+농도에 의존하지 않았다. PGE2에 의한 LHR기 분비와 CAMP합성은 PGE2농도(1$\times$10-7M-1$\times$10-4M)에 비례하여 촉진되었으며, $\beta$-endorphin (1x10-3M)은 PGEa에 의한 LHRH 분비촉진과 CAMP합성을 공히 억제하였다. 오피오이드 수용체의 길항제인 Naloxone(Ix10-"M)은 $\beta$-endorphin에 의한 저해효과를 극복시켜서, LHR광 분비와 CAMP합성은 각각 회복되었으나, CAMP합성은 부분적인 회복을 보인 반면에, LHRH분비는 PGE2에 의한 촉진효과보다도 더 활성화되었다. 결론적으로 LHRH분비에 미치는 오퍼오이드의 억제작용은 PGE2-cAMP의 세포내 전달과정을 저해함으로써 유발되는것으로 추정 된다.정 된다.

• The Korean Journal of Physiology
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• v.17 no.2
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• pp.135-142
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• 1983

$PGE_2$ and $PGF_{2{\alpha}}$ are known to act similarly in a number of animal tissues. They both facilitate regression of corpus luteum(Poyser, 1972; Fuch et al, 1974; Coudert et at, 1974) and stimulate contraction of uterine muscle (Laudanski et al, 1977; Porter et al, 1979; Hollingsworth et al, 1980). It is, however, not known whether these two prostaglandins exert similar actions in osmotic fragility of erythrocytes (Rasmussen et al, 1975) and $PGF_{2{\alpha}}$ alters conformation of membrane proteins (Meyers aud Swislocki, 1974). The former effect may not be mediated through changes in c- AMP concentration in the cell, since the adenylate cyclase activity in human erythrocyte is extremely low (Rodan et al, 1976; Sutherland et al, 1962) and the latter effect implies that physical state (or fluidity) of the membrane is altered by $PGF_{2{\alpha}}$. The present study was undertaken to elucidate mechanisms of action of $PGE_2$ and $PGF_{2{\alpha}}$ on the human erythocyte membrane by examining their effects on osmotic fragility and $Ca^{++}$ binding to the membrane fragments. The results are summarized as follows: 1) $PGE_2$ and $PGF_{2{\alpha}}$ increased osmotic fragility at concentrations above $10^{11}\;M$, the effect being similar for both hormones. The concentration of NaCl for 100% hemolysis was $1/16{\sim}1/17\;M$ in the presence of $10^{11}\;M\;PGE_2$ or $PGF_{2{\alpha}}$ and 1/18 M in the absence of the hormone (control). 2) When erythrocytes were suspended in 1/15 M NaCl solution, $44.2{\pm}4.3%$ of cells were hemolyzed. Addition of $10^{12}\;M\;PGE_2$ or $PGF_{2{\alpha}}$ did not increase hemolysis. When the concentration of the hormones was increased to $10^{11}\;M$, however the degree of hemolysis increased markealy to about 80%. No further increase in hemolysis was observed at concentration of the hormones above $10^{11}\;M$. 3) The additional hemolysis due to $10^{11}\;M\;PGE_2$ and $PGF_{2{\alpha}}$ appeared to he identical regardless of absence or presence of $Ca^{++}\;(0.5{\sim}10\;mM)$ in the suspending medium. 4) In the absence of prostaglandin, the binding of $Ca^{++}$ to the erythrocyte membrane increased curvilinearly as the $Ca^{++}$ concentration increased up to 5 mM above which it leveled off. A similar dependence of $Ca^{++}$ binding on the $Ca^{++}$ concentration was observed in the presence of $10^{11}\;M\;PGE_2$ or $PGF_{2{\alpha}}$, however, the amount of $Ca^{++}$ bound at a given $Ca^{++}$ concentration was significantly higher than in the absence of the hormones. 5) As in the hemolysis, $PGE_2$ and $PGF_{2{\alpha}}$ did not affect the $Ca^{++}$ binding at a concentration of $10^{12}\;M$, but increased it by about 100% at concentration above $10^{11}\;M$. These result indicate that both tile osmotic fragility of erythrocyte and the $Ca^{++}$ binding to the erythrocyte membrane are similarly enhanced by $PGE_2$ and $PGF_{2{\alpha}}$, but these two effects are not causally related. It is, therefore, concluded that the prostaglandin-induced hemolysis is not directly associated with alterations of the $Ca^{++}$ content in the membrane.