• Title/Summary/Keyword: 15-PGDH

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Extracellular Prostaglandin $E_2$ Upregulation Effect of the Methanol Extract of Artemisia argyi

  • Lee, Kyoung In;Moon, Young Sook;Pyo, Byoung Sik;Choi, Chul Hee
    • Natural Product Sciences
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    • v.18 no.4
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    • pp.211-214
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    • 2012
  • Since 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key metabolic enzyme of prostaglandin $E_2$ ($PGE_2$), inhibition of 15-PGDH is supposed to facilitate various physiological functions by increasing $PGE_2$. Methanol extract of Artemisia argyi (AAME) inhibited 15-PGDH ($IC_{50}$: $13.13{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$: $415.00{\mu}g/mL$) and elevated extracellular $PGE_2$ levels in HaCaT cells. Real-time PCR analysis showed that AAME decreased significantly mRNA expression of PG transporter (PGT) in HaCaT cells. These results indicate that AAME could be applicable to functional materials as a 15-PGDH inhibitor and PGT expression inhibitor for the upregulation of extracellular $PGE_2$ level.

15-Hydroxyprostaglandin dehydrogenase as a marker in colon carcinogenesis: analysis of the prostaglandin pathway in human colonic tissue

  • Yang, Dong-Hoon;Ryu, Yeon-Mi;Lee, Sun-Mi;Jeong, Jin-Yong;Yoon, Soon Man;Ye, Byong Duk;Byeon, Jeong-Sik;Yang, Suk-Kyun;Myung, Seung-Jae
    • Intestinal research
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    • v.15 no.1
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    • pp.75-82
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    • 2017
  • Background/Aims: Cyclooxygenase-2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and microsomal prostaglandin E synthase-1 (mPGEs-1) regulate prostaglandin $E_2$ ($PGE_2$) expression and are involved in colon carcinogenesis. We investigated the expression of $PGE_2$ and its regulating genes in sporadic human colon tumors and matched normal tissues. Methods: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of $PGE_2$ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively. Results: The expression of COX-2, mPGEs-1, and $PGE_2$ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001). In adenocarcinomas, mPGEs-1 and $PGE_2$ expression was significantly higher (P<0.001 and P=0.020, respectively), and COX-2 expression did not differ from that in normal tissues (P=0.207). 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018). Conclusions: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to $PGE_2$ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.

Development of a Coupled Enzyme Assay Method for Microsomal Prostaglandin E Synthase Activity

  • Choi, Kyung-A;Park, Sung-Jun;Yu, Yeon-Gyu
    • Bulletin of the Korean Chemical Society
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    • v.31 no.2
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    • pp.384-388
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    • 2010
  • Human microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of prostaglandin $H_2$ ($PGH_2$) into prostaglandin $E_2$ ($PGE_2$). To establish a stable and efficient method to assess the activity of mPGES-1, a coupled enzyme assay system using mPGES-1, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and phosphomolybdic acid (PMA) was developed. In this assay system, $PGH_2$ was converted to $PGE_2$ by mPGES-1, and then $PGE_2$ was further transformed to the 15-keto-$PGE_2$ by 15-PGDH accompanying the production of NADH, which was easily detected by fluorescence spectrometry in a multi-well plate format. During the reaction, spontaneous oxidation of $PGH_2$ was prevented by PMA. Using this novel assay, the $K_m$ value of mPGES-1 for $PGH_2$ and the $IC_{50}$ value of the previously characterized inhibitor, MK-886, were determined to be 0.150 mM and $2.8\;{\mu}M$, respectively, which were consistent with the previously reported values. In addition, low backgrounds were observed in the multi-wall plate screening of chemical compounds.

Molecular Cloning of the cCDNA for $NAD^+$ /-dependent 15-hydroxyprostagladin Dehydrogenase Gene Homologue from the Mole Cricket, Gryllotalpa orientalis

  • Kim, Iksoo;Lee, Young-Sin;Kim, Eun-Sun;Lee, Heui-Sam;Kim, Jin-Won;Ahn, Mi-Young;Ryu, Kang-Sun
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 2003.04a
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    • pp.67-67
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    • 2003
  • The NAD$^{+}$-dependent 15-hydroxyprostagladin dehydrogenase (15-PGDH) is a key catabolic enzyme responsible for the control of the biological activities of prostagladins. So far the gene has been found in a diverse organism including three insect dipteran species and one lepidopteran species. In this study, a cDNA encoding the 15-PGDH gene homologue was isolated from the cDNA library of the mole cricket, Gryllotalpa orientalis. (omitted)d)

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Biomarker-directed Targeted Therapy in Colorectal Cancer

  • John M. Carethers
    • Journal of Digestive Cancer Research
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    • v.3 no.1
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    • pp.5-10
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    • 2015
  • With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material. For CRC, current examples of biomarkers for screening and surveillance include germline testing for suspected hereditary CRC syndromes, and stool DNA tests for screening average at-risk patients. Molecular biomarkers for CRC that may alter patient care and treatment include the presence or absence of microsatellite instability, the presence or absence of mutant KRAS, BRAF or PIK3CA, and the level of expression of 15-PGDH in the colorectal mucosa. Molecularly targeted therapies and some general therapeutic approaches rely on biomarker information. Additional novel biomarkers are on the horizon that will undoubtedly further the approach to precision or individualized medicine.

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Prostaglandin E2 Up-regulation and Wound Healing Effect of the Ethanol Extract of Eriobotryae Folium in Human Keratinocyte (피부 각질세포에 대한 비파엽 에탄올 추출물의 PGE2 조절 작용과 상처치료 효과)

  • Im, Do Youn;Lee, Kyoung In
    • Korean Journal of Medicinal Crop Science
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    • v.22 no.6
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    • pp.457-462
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    • 2014
  • Prostaglandin (PG) $E_2$ is an important mediator of skin wound healing without excessive scarring and gastric ulcer healing. However, $PGE_2$ has a short lifetime in vivo because it is metabolized rapidly by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Ethanol extract of Eriobotryae folium (EFEE) elevated intracellular and extracellular $PGE_2$ levels in HaCaT cells and inhibited 15-PGDH ($ED_{50}$ : $168.4{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$ : $250.0{\mu}g/mL$). Real-time PCR analysis showed that mRNA expression of cyclooxygenase (COX)-1 and COX-2 enzymes were increased and prostaglandin transporter (PGT) was decreased in HaCaT cells by EFEE. Moreover, wound healing effect of EFEE ($168.4{\mu}g/mL$) was comparable to that of TGF-${\beta}1$ (300 pg/mL) as a positive control. These results demonstrate that EFEE may be valuable therapeutic materials for the treatment of $PGE_2$ level dependent diseases.

Allozyme Variability in Tree of Genus Semisulcospira(Prosobranchia: Pleuroceridae) (다슬기속 3종(Prosobranchia: Pleuroceridae)에서의 도위효소 변이)

  • 정영헌;박준우;정평림;박갑만;김재진;민득영
    • The Korean Journal of Malacology
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    • v.15 no.1
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    • pp.13-20
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    • 1999
  • A horizontal starch gel electrophoresis for enzyme proteins extracted from three Korean species and one Chinese species of Semisulcospira was carried out in order to elucidate their genetic relationships. A total of 10 enzymes were employed in three different of buffer systems. Two loci from each enzyme of GAPDH, GOT, ICDH, IDH and PEP(VL); three loci from each of three enzymes, EST, PEP(LGG) and PGDH; and five loci from GPI were observed. Most of the loci in three pleurocerid species employed showed homozygous monomorphic banding patterns and some of them were specific as genetic markers between two different species. However, EST-2, PEP(LGG-3) and PGDH-1 loci in Korean S. libertina and PEP(LGG-3), PGM-1 and PGM-2 loci in Chinese S. libertina showed polymorphic banding patterns. Three Korean Semisulcospira species including S. libertina were more closely clustered in a dendrogram within the range of genetic identity values of 0.818-0.936, and these clusters were lineated with Chinese S. libertina at the value of 0.621.

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Effects of Vegetable Sprout Power Mixture on Lipid Metabolism in Rats Fed High Fat Diet (새싹채소 혼합분말이 고지방 식이를 급여한 흰쥐의 지질대사에 미치는 영향)

  • Lee, Jae-Joon;Lee, Yu-Mi;Shin, Hyoung-Duck;Jeong, Young-Sim;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.8
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    • pp.965-974
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    • 2007
  • This study was performed to investigate the effects of vegetable sprout powder on serum and adipose tissue lipid metabolism in rats fed high-fat diet for 4 weeks for induction hyperlipidemic model rat. Weight-matched male Sprague-Dawley rats were assigned to five groups according to dietary fat level (10% or 20% of diet wt.) and mixture of vegetable sprout powder levels (5% or 10% 10% or 20% of diet wt.). Vegetable sprout powder was the mixture of same amounts of dried barley, broccoli, rapeseed, alfalfa, radish, mustard, buckwheat and brussels sprouts. Experimental groups were normal fat diet with 5% cellulose (NF-C), high fat diet without fiber (HF-N), high fat diet with 5% cellulose (HF-C), HF-C diet with 5% vegetable sprout powder (HF-CSL), and HF-C diet with 10% vegetable sprout powder (HF-CSH). The body weight of HF-N group increased 16% compared with the NF-C group, while it was decreased by 15% and 22% for HF-CSL group and HF-CSH group, respectively. Fat mass and fat cell size of adipose tissue were lower in HF-CSL group and HF-CSH group compared with HF-C group, and lower in HF-CSH group compared with HF-CSL group. Serum triglyceride, total cholesterol and LDL-cholesterol contents were markedly decreased by vegetable sprout powder containing diet, while the serum HDL-cholesterol and phospholipid contents were higher in vegetable sprout powder containing diet in a dose-dependent manner. Leptin and insulin levels in serum showed a decrease in HF-CSH group. Significantly increased contents of triglyceride, total cholesterol, LDL-cholesterol, leptin and insulin in the serum of HF-N group were returned to normal or even below normal levels by feeding 10% vegetable sprout powder diet. The increased activities of NADP-malate dehydrogenase (ME), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) and lipoprotein lipase (LPL) in adiposetissue by HF-N group were decreased to the activity of normal fat group by feeding vegetable sprout powder in a dose-dependant manner. These results indicate that lipid metabolism in rats fed high-fat diet was suppressed by feeding vegetable sprout powder.