• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.96-96
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• 2003

Acyl-CoA synthetase 4는 생쥐에 있어서 거의 모든 조직에서 발현하며 아라키돈산에 특이적인 효소이다. 아라키돈산은 세포막의 인지질로부터 cPLA2에 의하여 유리되고 cyclooxygenase-1, -2에 의하여 eicosanoid로 변환된다. 이렇게 생산된 prostaglandin과 같은 eicosanoid는 배란, 수정, 임신에 있어서 중요한 기능을 수행하고 있다. 그러나 세포막으로부터 유리된 아라키돈산은 acyl-CoA synthetase 4에 의하여 다시 세포막으로 재에스테르화되어 eicosaniod의 생산을 조절하는 것으로 생각되어지고 있다. 또한 acyl-CoA synthetase 4 유전자 한쪽이 knock-out된 heterozygote mouse에서는 사산, 유산과 난소에 있어서 황체 수의 증가 등을 보고하고 있다. 그러므로 본 연구에서는 정상 생쥐 (C57BL/6) 임신 기간 중 acyl-CoA synthetase 4 유전자의 발현을 확인하기 위하여 자궁, 난소, 태아에서 RT-PCR을 수행하였다. 또한 cPLA2, cyclooxygenase-1, cyclooxygenase-2 유전자의 발현 양상을 분석하여 eicosanoid 생산에 관여하는 유전자 상호간의 발현 을 확인하였다. acyl-CoA synthetase 4는 임신 0 day에서부터 19.5 day까지 자궁과 난소에서 모두 발현하고 있었다. 또한 5.5 day에서부터 19.5 day까지의 태아에서도 그 발현이 확인되었다. 그리고 cPLA2와 cyclooxygenase-1은 acyl-CoA synthetase 4와 유사한 양상을 보였으나 cyclooxygenase-2는 임신기간 중의 자궁, 난소, 태아에서 전혀 발현하지 않았다. 그러므로 임신 중 생쥐 자궁, 난소, 태아에 있어서 eicosanoid 생산에는 cPLA2, cyclooxygenase-1, acyl-CoA synthetase 4 유전자가 관여하고 있는 것으로 생각된다.

• BMB Reports
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• v.42 no.7
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• pp.401-410
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• 2009

We have developed a targeted lipidomics approach that makes it possible to directly analyze chiral eicosanoid lipids generated in cellular systems. The eicosanoids, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and alcohols (HETEs), have been implicated as potent lipid mediators of various biological processes. Enzymatic formations of eicosanoids are regioselective and enantioselective, whereas reactive oxygen species (ROS)-mediated formation proceeds with no stereo-selectivity. To distinguish between enzymatic and non-enzymatic pathways of eicosanoid formation, it is necessary to resolve enantiomeric forms as well as regioisomers. High sensitivity is also required to analyze the eicosanoid lipids that are usually present as trace amounts (pM level) in biological fluids. A discovery of liquid chromatography-electron capture atmospheric pressure chemical ionization/mass spectrometry (LC-ECAPCI/MS) allows us to couple normal phase chiral chromatography without loss of sensitivity. Analytical specificity was obtained by the use of collision-induced dissociation (CID) and tandem MS (MS/MS). With combination of stable isotope dilution methodology, complex mixtures of regioisomeric and enantiomeric eicosanoids have been resolved and quantified in biological samples with high sensitivity and specificity. Targeted chiral lipidomics profiles of bioactive eicosanoid lipids obtained from various cell systems and their biological implications have been discussed.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.67-73
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• 2007

There have been various inflammatory skin disorders in humans including atopic dermatitis, eczema and psoriasis. Although some drugs have been used for these disorders, there is an urgent need for safer and more effective topical anti-inflammatory agents. Plant flavonoids possess anti-inflammatory activity and some of them have multiple pharmacological mechanisms, inhibition of eicosanoid metabolizing enzymes, histamine release and/or down-regulation of pro inflammatory gene expression. These properties of flavonoids may be suitable for treating chronic skin inflammatory disorders. Especially, wogonin, some prenylated flavonoids and biflavonoids have a strong potential as new anti-inflammatory agents by topical application.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.526-531
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• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• Journal of Nutrition and Health
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• v.35 no.10
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• pp.1038-1044
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• 2002

The study was designed to observe the effect of conjugated linoleic acid (CLA) on tumor incidence, eicosanoid formation and antioxidant enzyme activities in colonic mucosa and the fecal excretion of deoxycholic acid and lithocholic acid in 1,2-dimethylhydrazine (DMH)-treated rats. One hundred twenty male Sprague Dawley rats were divided into 2 groups, BT (beef tallow diet) group and FO (fish oil diet) group, and each group was again subdivided into 2 groups depending on CLA supplementation, i.e.4 groups of BT, BTC, FO, FOC. All rats were fed experimental diet for 30 weeks, which contained 12% (wt/wt) total dietary fat including 1% (wt/wt) CLA, and were intramuscularly injected with DMH for 6 weeks to give total dose of 180 mg/kg body. CLA-supplemented to BT and FO diet reduced tumor incidence, eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. N-3 fatty acids (mainly DHA) of fish oil diet (FO, FOC group) also reduced tumor incidence and significantly reduced eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. CLA supplementation and n-3 fatty acid significantly increased colonic mucosal level of superoxide dismutase and glutathione peroxidase activities but reduced secondary bile acids (deoxycholic acid and lithocholic acid) excretion in the feces. In conclusion, CLA supplementation and n-3 fatty acid could reduce tumor incidence by reducing eicosanoids and increasing antioxidant enzyme activities in colon and decreasing the excretion of deoxycholic acid and lithocholic acid in the feces. The data might suggest that CLA supplementation and n-3 DHA rich fish oil may modulate colon carcinogenesis.termediate level of endurance exercise training for 6 weeks did not influence concentrations of most of free amino acid in soleus muscle of rats collected at an overnight fasted and rested state. In contrast, isolucine and leucine concentrations in extensor digitorum longus muscle of exercise-trained rats were significantly lower than those for control animals. These results indicate that aerobic energy metabolism had not been efficiently conducted, and thereby the utilization of BCAA for energy substrate was enhanced in fast twitch oxidative glycolytic fibers of extensor digitorum longus muscle of rats followed exercise-training protocol for 6 weeks.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.153-153
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• 1993

Prostaglandin은 인체의 여러 조직에서 생성되어 체내에 널리 분포되어 있지만 그 함유량은 극히 적다. 또한 대사산물의 반감기가 매우 이에 대한 연구결과를 알기 위하여는 조직 또는 체액을 추출하여 세심한 주의가 필요하고 측정방법에 있어서 정밀성이 요구된다. 또 여러가지 대사산물과 전구물질을 분리할 수 있는 방법이 요구된다. Prostaglandin가 생성되고 대사되는 과정이 매우 복잡하기 때문에 보다 정확하게 여러가지 대사산물을 분리할 수 있는 방법이 요구된다. 한편, prostaglandin은 전신의 거의 모든 조직에 분포하며 그 이용도 다양하다. 뿐만 아니라, prostaglandin이 임상적으로 생체기능의 조절(고혈압, 신기능조절, 난소와 자궁의 생리 등) 및 prostaglandin analogue의 길항약물 및 생합성 억제약물로서도 중요한 의미를 가지고 있다. 본 연구에서는 이러한 관점에서 prostaglandin을 측정하는데 있어서: 1. 조직의 추출과 조작에 대한 일반적 방법 2. 생체조직에서 eicosanoid의 추출 방법 3. Prostaglandin, thromboxane 및 leukotriene에 대하여 평활근을 이용한 생물학적 검정 4. Eicosanoids의 방사면역학적 검정 5. 효소면역 검정법 6. Cyclooxygenase의 측정, 정체 및 특성 7. Lipoxygenase의 특성과 측정 8. 지질과산화 반응의 측정 등을 다루었다.

• Journal of Nutrition and Health
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• v.31 no.1
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• pp.21-27
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• 1998

The objective of this study was to observe the effect of dietary calcium(Ca) level on colonic mucosal levels of cell proliferation, 1, 2-diacylglycerol(DAG), TXB2, PGE2 and phospholipid fatty acid composition which have been known as biomarkers for colon cancer. One hundred male Sprague Dawley rats, at 7 weeks of age, were divided into two fat type groups. Each group of which was further divided into two Ca level groups. Each rt was intramuscularly injected with 1, 2,-dimenthylhydrazine(DMH) for 6 weeks (total dose of 180mg/kg body weight) and simultaneously fed one of four experimental diets containing 15% dietary fat(corn oil or perilla oil )and 0.3% or 1.0% Ca by weight for 20 weeks. Compared to corn oil, perilla oil significantly reduced cell proliferation by decreasing labeling index, proliferating zone, crypt length in colonic mucosa and colonic mucosa and colonic mucosal levels of DAG, TXB2 . PGE2 and phospolipid (PL) arachidonic acid distribution. The effect of Ca on biomarketrs was different depending on the type of dietary fat comsumed . Ca effect of Ca on biomarkers was different depending on the type of dietary fat comsumed. Ca effect was not significantly shown in the PO group, but it was significant in the CO group in which high Ca(1.0%) decreased the levels of levels of PL-C20 : 4(%), DAG and PGE2 . However , high Ca supplementation had shown only the trends of improving cell proliferation. Overall , high dietary Ca significantly reduced cell proliferation by inhibiting the synthesis of eicosanoid and DAG with reduced distribution of PL-C20 : 4 , which may have resulted in lower activation of PKC through reduced signal transduction. Since a high level of dietary Ca was more effective in reducing the risk factor against colon cancer in corn oil fed rats, it could be suggested that a higher amount of dietary Ca be consumed , especially when more vegetable oil rich in linoleic acid is included in the diet.

• Journal of Nutrition and Health
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• v.25 no.5
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• pp.351-359
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• 1992

This study was conducted to compare the effects of perilla oil or corn oil on lipid peroxidation and eicosanoid productions which are associated with the promotion of carcinogenesis. in liver or blood in rats. Male Sprague-Dawley8 weaning rats were fed on semisynthetic diets containing 15%(w/w) beef fat(BF). corn oil(CO) or perilla oil(PO) Three weeks after the half of rats in each diet group were injected with a single dose of 50mg 2-acetylaminofluorene (AAF)/Kg BW hepatocarcinogen intraperitoneally 3 times at 2-day interval and all of the rats were sacrificed after 8 weeks from the first injection. The rats fed on different dietary fats without 2-AAF treatment had not different MDA produc-tion and conjugated diene content in liver microsome. CO+AAf group had significantly higher conjugated diene content than BF+AAF and PO+AAF groups. and lower glucose-6-phospha-tase activity than BF+AAF group But PO+AAF had similar conjugated diene content to BF+AAF group and significantly lower MDA production than BF+AAF and CO+AAF groups. The hepatic mocrosomal lipid peroxidation was slightly greater in CO group than in PO group though perilla oil(P/S=9.67) has much more polyunsaturated fatty acids than corn oil(P/S=2.92) PG E2 level in liver and TX B2 level in plasma were significantly higher in CO group than in BF and PO groups. TX B2 level was lowered in CO and BF groups by 2-AAF treatment. These results reach to the contclousion than the type of dietary fatty acid as well as the P/S ratio has effect on hepatic microsomal lipid peroxidation and eicosanoid production and perilla oil or linolenic acid(n3) might be less effective on lipid peroxidation or PG E2 and TX B2 mediated tumor promotion than corn oil or linoleic acid(n6).

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.525-530
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• 2000

During reperfusion of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids, are released and may have a role in the pathogenesis of reperfusion injury. To validate the role of eicosanoids in the ischemia-reperfusion induced functional deficits in skeletal muscle, we compared muscle edema and the changes of eicosanoid concentration in the rat hind limb after ischemia-reperfusion injury by application of tourniquet. After 4 hours of ischemia, reperfusion was established for 4 hours by releasing tourniquet. To assess tissue damage, edema, and wet/dry weight ratios were determined and the eicosanoid concnentrations were measured by the HPLC. The muscle edema and the release of cyclooxygenase metabolites were not induced by the ischemia itself rather they were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema and decreased the release of $6-keto-PGF_{1{\alpha}},$ thromboxane $B_2,$ and $PGE_2$ inducedby reperfusion. But the inhibitory effect of indomethacin on edema (35%) was relatively low than the inhibitory effect on release of cyclooxygenase metabolites (up to 69%) by reperfusion. These results support the view that cyclooxygenase products may play a significant role in the formation of muscle injury by ischemia-reperfusion and suggest that nonsteroidal antiinflammatory agents might be partially beneficial to the management of acute limb ischemia-reperfusion injury.

• Korean journal of applied entomology
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• v.51 no.4
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• pp.349-356
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• 2012

Eicosanoid mediates various cellular immune responses in insects. This study aimed to discover its novel action on the modulation of hemocyte populations in response to an immune challenge. Upon bacterial challenge, the last instar larvae of the beet armyworm, Spodoptera exigua, increased their total hemocyte density in 2 h, and then decreased it to a basal hemocyte density level. This rapid increase in total hemocyte density was explained by an increase of plasmatocyte and spherulocyte densities. When larvae were treated with dexamethasone (a specific phospholipase $A_2$ ($PLA_2$) inhibitor), they did not show any increase in hemocyte density in response to bacterial challenge. However, the addition of arachidonic acid (a catalytic product of $PLA_2$) to larvae treated with dexamethasone recovered the up-regulation of hemocyte density in response to bacterial infection. Among eicosanoid, cyclooxygenase (COX), but not lipoxygenase (LOX), products seemed to mediate the increase of hemocyte density in response to bacterial infection because naproxene (a COX inhibitor) inhibited the hemocyte density increase, though esculetin (a LOX inhibitor) did not. Prostaglandin $E_2$, a COX product, significantly increased the hemocyte density even without bacterial infection. These results suggest that eicosaniod mediates a rapid increase in total hemocyte density in response to immune challenge.