• Biomolecules & Therapeutics
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• 제9권2호
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• 한국환경보건학회지
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• 제32권6호
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• pp.566-570
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• 2006

Exposure to ultraviolet B(UVB) radiation causes skin inflammation such as pigmentation and the induction of cyclooxygenase-2(COX-2) gene expression. In this study, we investigated the effect of natural extracts from Tea, EGb 761 and Korean red ginseng(KRG), on the pigmentation and expression of COX-1 and COX-2 mRNA in UVB-irradiated C57BL/6 mice. Before UVB irradiation, the skin color was significantly showed the lightening effect by topical application of natural compounds (p<.05). In the case of UVB irradiated mice, we observed a decrease in pigmentation by compounds (p<.05). In irradiated skin, COX-1 mRNA expression is not changed following UVB irradiation, but COX-2 gene increases. Also, natural compounds lowered mRNA levels of COX-2. Therefore, these results suggest that COX-2 mRNA increases by UVB irradiation. Also, Tea, EGb 761 and KRG as a topical application may inhibit skin pigmentation and modulate COX-2 mRNA level.

• 약학회지
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• 제43권6호
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• pp.776-781
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• 1999

Dockings of 4,5-diarylpyrroles into cyclooxygenase-1 and cyclooxygenase-2 were carried out by GOLD program. The sulfonyl groups bonded to 5-phenyl ring of 4,5-diarylpyrroles are directed to Arg513 of COX-2 and Tyr385 of COX-2 docking modes of pyrroles are different from COX-1. Tyr385 and Arg120 of COX-1 and COX-2 have been recognized as important residues. Val523 of COX-2 may be also important. A new COX-2 selective inhibitors could be designed from the docking study.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.114-121
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• 2023

선택적 cyclooxygenase (COX)-2 억제제는 기존의 비스테로이드성 소염제의 위장 부작용을 줄일 수 있는 새로운 대체제이다. 하지만, 최근 혈전을 일으켜 심혈관 질환의 위험을 증가시킨다는 보고가 있다. 따라서 본 연구에서는 유효성분인 ursolic acid를 각각 40, 50%로 극대화한 로즈마리 추출물(RE)의 항염증 효과와 이에 따른 심혈관 부작용의 안전성을 확인하였다. RE의 COX 효소 활성 저해 평가 결과 40, 50% RE는 100 ㎍/mL에서 양성 대조군인 celecoxib 및 rofecoxib와 비슷한 COX-2 저해 활성을 보였고, COX-1 저해 활성은 미미하였다. 이후 Lipopoly-saccharide (LPS)를 조건에 따라 처리한 RAW 264.7 세포에 40, 50% RE 1 ㎍/mL를 처리하여 COX-2, COX-1 유전자 발현, 세포 배양액의 prostaglandin E₂ (PGE₂), thromboxane B₂ (TXB₂) 농도를 확인하였다. 실험 결과 COX-2 유전자 발현은 40% RE가 LPS를 24시간 후처리한 조건에서 감소하였고, 40, 50% RE는 COX-1 유전자 발현 및 PGE₂, TXB₂ 농도에는 유의한 영향을 주지 않는 것으로 확인되었다. 따라서 RE는 혈전 생성에 관여하는 prostaglandins의 균형에 영향을 주지 않아 심혈관 혈전 생성의 위험성이 적을 것으로 사료된다.

• 한국어병학회지
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• 제26권1호
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• pp.19-30
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• 2013

Megalocytivirus는 우리나라를 포함한 아시아 각국의 양식현장에서 고위험성 병원체이다. 그럼에도 불구하고 어류의 면역체계와 megalocytivirus의 상호관계에 관한 연구는 아직 부족한 실정이다. 다양한 연구에서 cyclooxygenase isoform중 COX-1 유전자는 constitutive 하게 발현되며, COX-2 enzyme은 면역반응에 중요한 역할을 한다고 알려져 있다. 또한 COX-2 유전자는 LPS (lipopolysaccharide) 또는 병원체의 감염과 같은 염증반응 시 그 발현이 증가한다고 알려져있다. 본 연구는 다른 어종의 COX-2 유전자를 바탕으로 제작된 degenerated primer와 5'- 그리고 3'-end RACE-PCR을 이용하여 돌돔에서 COX-2 유전자의 전체 염기서열을 밝혔으며, 그 결과 rbCOX-2 (rock bream COX-2)유전자 cDNA의 전체 길이는 2655 bp 였으며, 609개의 아미노산으로 구성되어있었다. rbCOX-2 유전자의 genomic organization은 9개의 intron과 10개의 exon으로 구성되어 있었다. 또한 본 연구에서는 돌돔에 megalocytivirus의 인위감염 시 COX-2 유전자의 발현을 조사하였다. LPS 접종 시 rbCOX-2 유전자는 접종 1일 후 대조구와 비교하여 13.10배 증가하여 최고 발현을 보였으나, megalocytivirus 접종 시 대조구와의 비교에서 유의적인 발현을 확인할 수 없었다. 돌돔에서 COX-2 유전자의 염기서열의 분석과 발현 분석은 바이러스 감염 시 어류의 방어기작을 이해하는데 도움이 될 것이며, 바이러스 백신개발 및 치료제 개발의 기초자료로 활용될 것이다.

• Tuberculosis and Respiratory Diseases
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• 제67권4호
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• pp.303-310
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• 2009

Background: Elevated expression of cyclooxygenase-2 (COX-2) and Polo-like kinase-1 (PLK-1) is observed in a wide variety of cancers. Augmented expression of COX-2 and enhanced production of prostaglandin $E_2(PGE_2)$ are associated with increased tumor cell survival and malignancy; COX-2 has been implicated in the control of human non-small cell lung carcinoma (NSCLC) cell growth. PLK-1 siRNA induced the cell death of lung cancer cells and the systemic administration of PLK-1 siRNA/atelocollagen complex inhibited the growth of lung cancer in a liver metastatic murine model. COX-2 and PLK-1 are involved in proliferation and in cell cycle regulation, and there is a significant correlation between their interaction in prostate carcinoma. Methods: In this study, we investigated the pattern of COX-2 and PLK-1 expression in NSCLC, after treatment with IL-1$\beta$, COX-2 inhibitor and PLK-1 siRNA. Results: Expression of PLK-1 was decreased in A549 COX-2 sense cells, and was increased in A549 COX-2 anti-sense cells. Knock out of PLK-1 expression by PLK-1 siRNA augmented COX-2 expression in A549 and NCl-H157 cells. When A549 and NCI-H157 cells were treated with COX-2 inhibitor on a dose-dependent basis, PLK-1 and COX-2 were reduced. However, when the expression of COX-2 was induced by IL-1$\beta$, the production of PLK-1 decreased. Conclusion: These results demonstrate that COX-2 and PLK-1 are regulated and inhibited by each other in NSCLC, and suggest that these proteins have a reverse relationship in NSCLC.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.103-104
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• 2002

Cyclooxygenase (COX), an important enzyme involved in mediating the inflammation, catalyzes the rate-limiting step in the formation of prostaglandins from arachidonic acid. There are two isoforms of COX, designated as COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 can be induced transiently by proinflammatory cytokines, endotoxins, growth factors, oncogenes, UV and mitogens.(omitted)

• Molecules and Cells
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• 제22권1호
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• pp.44-50
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• 2006

We investigated the possible role of p38 MAPK and $ET_B$ receptors in ET-1 induction of cyclooxygenase-2 (COX-2) and prostaglandin $E_2$ ($PGE_2$) in cultured feline esophageal smooth muscle cells (ESMC). Confluent layers of ESMC were stimulated with 10 nM ET-1 and expression of COX-1 and COX-2, involvement of receptors, and activation of p38 MAPK, were examined by Western blot analysis. Levels of $PGE_2$ induced by ET-1 were measured by Elisa. Using $ET_A$and $ET_B$ antagonists (BQ-123 and BQ-788, respectively), the contribution of the ET receptors to COX-1 and COX-2 expression induced by ET-1 was determined. Western blot analysis revealed that treatment of ESMC with ET-1 resulted in transient expression of COX-2 and activation of p38 MAPK. Activation of p38 MAPK was maximal after 1 h. SB202190, a p38 MAPK inhibitor, reduced expression of COX-2, but not COX-1. ET-1-induced release of $PGE_2$ was also blocked by SB202190. COX-2 expression was upregulated only via the $ET_B$ receptor, and COX-1 expression was not affected by either antagonist. Taken together, our data suggest that ET-1 causes p38 MAPK-dependent expression of COX-2 by interacting with $ET_B$ receptors on ESMC.

• 약학회지
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• 제46권6호
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• pp.375-380
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• 2002

In this study, newly designed COX-2 inhibitors, synthetic derivatives of benzothiazine-3-carboxamide, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. 7-Bromo-1,2-benzoisothiazine derivatives were obtained from 4-bromotoluene over the chlorosulfonation, amination and oxidation. And benzothiazine ring was synthesized through Gabriel-Colmann rearrangement reaction. To evaluate inhibitory effect of COX-2, synthetic derivatives of benzothiazine-3-carboxamide were tested with accumulation of prostaglandin by lipopolysaccharide in aspirin-treated murine macropharge cell. Some of the synthesized lead compounds have potentially shown the structure-activity relationship for selectivity of COX-2 inhibition activity.

• Clinical and Experimental Reproductive Medicine
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• 제25권1호
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• pp.25-33
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• 1998

Cyclooxygenase (COX) is an enzyme involved in the conversion of arachidonic acid to prostaglandins (PGs), and exists in two forms, COX-1 and COX-2. COX has been reported to be involved in early implantation by secretion of PGs which causes permeability of vessels and reaction of decidual cells around the implantation site. Recently, in mice and sheep studies, COX-1 and COX-2 expression in the endometrium has been reported to be different according to implantation and stages of the estrous cycle, but expression of COX-1 and COX-2 in human endometrium during the menstrual cycle has not yet been established. The purpose of this study was to observe the variances of COX-1 and COX-2 expression by immunohistochemical staining in endometrial samples obtained from human hysterectomy specimens and biopsies of women of reproductive age according to different stages of the menstrual cycle. Also, we attempted to observe COX-1 and COX-2 expression in the epithelial and stromal cells of the endometrium obtained during the mid-secretory phase, which were cultured separately. COX-2 showed a cyclic pattern of expression according to the different stages of the menstrual cycle and was strongly expressed particularly at the mid-secretory phase which corresponds to the time of implantation. However, COX-1 tended to be increased in the early proliferative, and mid- and late secretory phases, but was also expressed in the whole menstrual cycle showing no particular pattern. In the separately cultured cells COX-1 was expressed in epithilial cells and COX-2 in the stromal cells. The above results suggest that since COX-2 is expressed at the same time as implantation and cultured cells display a specific secretory pattern, COX-2 has inductive endocrine enzyme properties and has an important effect on endometrial cells during implantation. Also, COX-2 expression in endometrial cells may be utilized as a useful marker of endometrial maturation.