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Hsin-hsiung Tai - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and biological evaluation of novel thiazolidinedione analogues as 15-Hydroxyprostaglandin Dehydrogenase inhibitors.
Journal of medicinal chemistry, 2011Co-Authors: Sandeep Karna, Hsin-hsiung Tai, Cheol Hee Choi, Min Tong, Chul Ho Jang, Hoon ChoAbstract:Novel thiazolidinedione analogues as 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) inhibitors were synthesized. Compounds 2, 3, and 4 exhibited IC(50) of 25, 8, and 19 nM, respectively. They also significantly increased levels of PGE(2) in A549 cells. To assess the influence of 15-PGDH inhibitor on cochlear blood flow (CBF), 2 was applied intravenously to guinea pigs. It increased their CBFs. Scratch wounds were also analyzed in confluent monolayers of HaCaT cells. Cells exposed to 4 showed significantly improved wound healing with respect to a control.
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15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Gastric Cancer
Clinical cancer research : an official journal of the American Association for Cancer Research, 2009Co-Authors: Alexandra Thiel, Hsin-hsiung Tai, Aparna Ganesan, Johanna Mrena, Siina Junnila, Antti I. Nykänen, Annabrita Hemmes, Outi Monni, Arto Kokkola, Caj HaglundAbstract:Purpose: We have investigated the expression and regulation of 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) in gastric cancer. Experimental Design: Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1β (IL-1β) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines. Results: In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2′-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1β repressed expression of 15-PGDH mRNA and protein. This effect of IL-1β was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E 2 production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues ( n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas ( n = 210). Conclusions: 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1β, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.
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nonsteroidal anti inflammatory drugs suppress glioma via 15 Hydroxyprostaglandin Dehydrogenase
Cancer Research, 2008Co-Authors: Naoki Wakimoto, Hsin-hsiung Tai, Ido Wolf, Dong Yin, James Okelly, Tadayuki Akagi, Lilach Abramovitz, Keith L Black, Phillip H KoefflerAbstract:Studies have conjectured that nonsteroidal anti-inflammatory drugs (NSAID) inhibit growth of various malignancies by inhibiting cyclooxygenase-2 (COX-2) enzyme activity. Yet, several lines of evidence indicate that a COX-2-independent mechanism may also be involved in their antitumor effects. Here, we report that NSAIDs may inhibit the growth of glioblastoma multiforme (GBM) cells through COX-2-independent mechanisms, including up-regulation of both 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH, the key prostaglandin catabolic enzyme) and the cell cycle inhibitor p21. Using Western blot and real-time PCR analysis in various GBM cell lines, we observed up-regulation of 15-PGDH and p21 after NSAIDs treatment. To elucidate the role of 15-PGDH in GBM, transfection assays were conducted using the T98G GBM cell line. Overexpression of 15-PGDH suppressed cell growth and was associated with increased expression of p21. In an attempt to investigate the roles of COX-2, 15-PGDH, and p21 in the inhibition of growth of GBM, small interfering RNA (siRNA) against each of these proteins was transfected into T98G cells. Inhibition of growth mediated by NSAIDs was partially reversed after knockdown of either 15-PGDH or p21, but not after COX-2 knockdown. Moreover, expression level of p21 was not affected in COX-2 siRNA transfected cells. Our studies provide evidence that the up-regulation of 15-PGDH induced by NSAIDs has the potential to inhibit growth of GBM, in part, by up-regulation of p21 possibly independent from COX-2 enzymatic function.
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15 Hydroxyprostaglandin Dehydrogenase 15 pgdh and lung cancer
Prostaglandins & Other Lipid Mediators, 2007Co-Authors: Hsin-hsiung Tai, Min Tong, Yunfei DingAbstract:15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) catalyzes NAD+-linked oxidation of 15 (S)-hydroxyl group of prostaglandins and lipoxins and is the key enzyme responsible for the biological inactivation of these eicosanoids. The enzyme was found to be under-expressed as opposed to cyclooxygenase-2 (COX-2) being over-expressed in lung and other tumors. A549 human lung adenocarcinoma cells were used as a model system to study the role of 15-PGDH in lung tumorigenesis. Up-regulation of COX-2 expression by pro-inflammatory cytokines in A549 cells was accompanied by a down-regulation of 15-PGDH expression. Over-expression of COX-2 but not COX-1 by adenoviral-mediated approach also attenuated 15-PGDH expression. Similarly, over-expression of 15-PGDH by the same strategy inhibited IL-1β-induced COX-2 expression. It appears that the expression of COX-2 and 15-PGDH is regulated reciprocally. Adenoviral-mediated transient over-expression of 15-PGDH in A549 cells resulted in apoptosis. Xenograft studies in nude mice also showed tumor suppression with cells transiently over-expressing 15-PGDH. However, cells stably over-expressing 15-PGDH generated tumors faster than those control cells. Examination of different clones of A549 cells stably expressing different levels of 15-PGDH indicated that the levels of 15-PGDH expression correlated positively with those of mesenchymal markers, and negatively with those of epithelial markers. It appears that the stable expression of 15-PGDH induces epithelial-mesenchymal transition (EMT) which may account for the tumor promotion in xenograft studies. A number of anti-cancer agents, such as transforming growth factor-β1 (TGF-β1), glucocorticoids and some histone deacetylase inhibitors were found to induce 15-PGDH expression. These results suggest that tumor suppressive action of these agents may, in part, be related to their ability to induce 15-PGDH expression.
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15-Hydroxyprostaglandin Dehydrogenase protein expression in human fetal membranes with and without subclinical inflammation.
Reproductive sciences (Thousand Oaks Calif.), 2007Co-Authors: Rose M. Rizek, Hsin-hsiung Tai, John R. G. Challis, Carole S. Watson, Sarah Keating, Alan D. BockingAbstract:Prostaglandins play a central role in the stimulation and maintenance of both term and preterm labor. 15-Hydroxyprostaglandin Dehydrogenase (PGDH), localized primarily to chorion trophoblasts, is the key enzyme responsible for the metabolism of prostaglandins. In preterm chorion, levels of PGDH protein and activity were lower when compared to term and were further reduced with the presence of infection, but effects of subclinical inflammation and membrane rupture on PGDH expression are not known. Our objectives were (1) to determine the relative expression of PGDH in amnion and chorion and (2) to determine the effect of preterm premature rupture of membranes (PPROM) and (3) subclinical inflammation on PGDH protein expression in preterm fetal membranes. Fetal membranes were collected from women with idiopathic preterm labor. Patients were divided into preterm birth (1)
Charles Mark Ensor - One of the best experts on this subject based on the ideXlab platform.
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Characterization of the Genomic Structure and Promoter of the Mouse NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase Gene ☆ ☆☆
Biochemical and biophysical research communications, 1997Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:Abstract The mouse NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) gene and its 5′-flanking region was cloned from a 129 mouse ES bacteriophage P1 genomic library. The gene contains 7 exons and 6 introns and is 11.3 kb in length. The transcription initiation site was mapped at 35 bases upstream from the ATG start codon. The nucleotide sequence of the 1.6 kb promoter region contains two TATA boxes and a number of potential regulatory elements including Sp1, CRE, GRE, AP1, AP2, NF-IL6 and estrogen receptor binding site. Studies of the promoter's activity showed that the first 400 nucleotides of 5′-flanking region efficiently drove the transcription of the luciferase reporter gene in U936 cells upon stimulation with a phorbol ester.
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characterization of the genomic structure and promoter of the mouse nad dependent 15 Hydroxyprostaglandin Dehydrogenase gene
Biochemical and Biophysical Research Communications, 1997Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:Abstract The mouse NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) gene and its 5′-flanking region was cloned from a 129 mouse ES bacteriophage P1 genomic library. The gene contains 7 exons and 6 introns and is 11.3 kb in length. The transcription initiation site was mapped at 35 bases upstream from the ATG start codon. The nucleotide sequence of the 1.6 kb promoter region contains two TATA boxes and a number of potential regulatory elements including Sp1, CRE, GRE, AP1, AP2, NF-IL6 and estrogen receptor binding site. Studies of the promoter's activity showed that the first 400 nucleotides of 5′-flanking region efficiently drove the transcription of the luciferase reporter gene in U936 cells upon stimulation with a phorbol ester.
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Cloning and expression of the cDNA for rat NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase.
Gene, 1997Co-Authors: Hongxing Zhang, Muneaki Matsuo, Charles Mark Ensor, Huiping Zhou, Hsin-hsiung TaiAbstract:Abstract The cDNA for rat NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) was cloned from an intestinal cDNA library. The sequence of this cDNA was found to be identical to that of the reverse transcription-polymerase chain reaction (RT-PCR) product obtained using rat lung RNA as a template. The cDNA contains a 798-bp open reading frame that codes for a protein of 266 amino acids (Mr 28 775) which shares 88.7% identity with the human 15-PGDH and 92.1% identity with the mouse 15-PGDH protein. The regions that are believed to be the NAD+ binding domain and the active site are conserved in the enzymes from the three different species. However, the sequence of the C-terminal 9 amino acids appears to be significantly different. The authenticity of the rat cDNA was confirmed by the expression of an enzymatically active 15-PGDH in E. coli.
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Cloning and expression of the cDNA for mouse NAD(+)-dependent 15-Hydroxyprostaglandin Dehydrogenase.
Biochimica et biophysica acta, 1996Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:The cDNA for mouse NAD+ dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) was isolated from a lung cDNA library. The cDNA contains a 798 bp open reading frame that codes for a protein of 266 amino acids (Mr 28 775) which shares 87% identity with the human 15-PGDH protein. The regions that are believed to form the NAD+ binding site and the active site are conserved in the mouse and human enzymes. The authenticity of the mouse cDNA was confirmed by expression of an active 15-PGDH inEscherichia coli. Northern blot analysis demonstrated that 15-PGDH mRNA is expressed primarily in lung, intestine, stomach and liver.
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Site-directed mutagenesis of the conserved serine 138 of human placental NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase to an alanine results in an inactive enzyme.
Biochemical and biophysical research communications, 1996Co-Authors: Charles Mark Ensor, Hsin-hsiung TaiAbstract:Human placental NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) is a member of the short-chain Dehydrogenase family of enzymes. It has been proposed that a highly conserved serine residue (corresponding to serine 138 of 15-PGDH) may be involved in the catalytic mechanism of many of these enzymes. Site-directed mutagenesis was used to change serine 138 of NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase to an alanine. The mutant protein was then expressed in E. coli. Western blot analysis indicated that the S138A mutant protein was expressed at levels similar to the wild type enzyme; however, the mutant protein was found to be inactive. These results support the proposed role of this highly conserved serine in enzyme activity.
J R Challis - One of the best experts on this subject based on the ideXlab platform.
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Activity and expression of 15-Hydroxyprostaglandin Dehydrogenase in cultured chorionic trophoblast and villous trophoblast cells and in chorionic explants at term with and without spontaneous labor.
American journal of obstetrics and gynecology, 2000Co-Authors: F Pomini, F A Patel, S Mancuso, J R ChallisAbstract:The aim of this study was to investigate whether any changes occurred at term before and with labor in the 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid level and in the 15-Hydroxyprostaglandin Dehydrogenase activity in cultured chorionic and villous trophoblast cells and in chorionic explants. Twelve placentas (labor group [vaginal delivery], n = 6; nonlabor group [elective cesarean delivery], n = 6) were collected. Chorionic trophoblast and villous trophoblast cells and chorionic disks were obtained, cultured, and incubated with 282-nmol/L prostaglandin F(2)(alpha). Medium was collected to measure the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha), and the cells and disks were snap-frozen to quantify 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid expression by Northern blot analysis. The formation of the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha) was significantly lower in the labor group than in the nonlabor group for both sets of cultured cells and for chorionic explants. 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid expression was lower in the chorionic trophoblast cells and chorionic disks of the labor group than those of the nonlabor group. However, the 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid level in the villous trophoblast cells did not differ between the labor and nonlabor groups. Prostaglandin metabolic activity in the chorion is reduced significantly at the time of labor.
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Activity and expression of 15-Hydroxyprostaglandin Dehydrogenase in cultured chorionic trophoblast and villous trophoblast cells and in chorionic explants at term with and without spontaneous labor.
American Journal of Obstetrics and Gynecology, 2000Co-Authors: F Pomini, F A Patel, S Mancuso, J R ChallisAbstract:Abstract Objective: The aim of this study was to investigate whether any changes occurred at term before and with labor in the 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid level and in the 15-Hydroxyprostaglandin Dehydrogenase activity in cultured chorionic and villous trophoblast cells and in chorionic explants. Study Design: Twelve placentas (labor group [vaginal delivery], n=6; nonlabor group [elective cesarean delivery], n=6) were collected. Chorionic trophoblast and villous trophoblast cells and chorionic disks were obtained, cultured, and incubated with 282-nmol/L prostaglandin F 2 α . Medium was collected to measure the 13,14-dihydro-15-keto metabolite of prostaglandin F 2 α , and the cells and disks were snap-frozen to quantify 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid expression by Northern blot analysis. Results: The formation of the 13,14-dihydro-15-keto metabolite of prostaglandin F 2 α was significantly lower in the labor group than in the nonlabor group for both sets of cultured cells and for chorionic explants. 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid expression was lower in the chorionic trophoblast cells and chorionic disks of the labor group than those of the nonlabor group. However, the 15-Hydroxyprostaglandin Dehydrogenase messenger ribonucleic acid level in the villous trophoblast cells did not differ between the labor and nonlabor groups. Conclusion: Prostaglandin metabolic activity in the chorion is reduced significantly at the time of labor. (Am J Obstet Gynecol 2000;182:221-6.)
Tianxin Yang - One of the best experts on this subject based on the ideXlab platform.
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Postnatal regulation of 15-Hydroxyprostaglandin Dehydrogenase in the rat kidney
American journal of physiology. Renal physiology, 2014Co-Authors: Ying Liu, Zhanjun Jia, Ying Sun, Li Zhou, Maicy Downton, Ren Chen, Aihua Zhang, Tianxin YangAbstract:Cyclooxygenase 2 (COX-2) has an established role in postnatal kidney development. 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) is recently identified as an endogenous inhibitor of COX-2, limiting the production of COX-2-derived prostanoids in several pathological conditions. The present study was undertaken to examine the regulation of renal 15-PGDH expression during postnatal kidney development in rats compared with COX-2. qRT-PCR and immunoblotting demonstrated that 15-PGDH mRNA and protein in the kidney were present in neonates, peaked in the second postnatal week, and then declined sharply to very low level in adulthood. Immunostaining demonstrated that at the second postnatal week, renal 15-PGDH protein was predominantly found in the proximal tubules stained positive for Na/H exchanger 3 and brush borders (periodic acid-Schiff), whereas COX-2 protein was restricted to macular densa and adjacent thick ascending limbs. Interestingly, in the fourth postnatal week, 15-PGDH protein was redistributed to thick ascending limbs stained positive for the Na-K-2Cl cotransporter. After 6 wk of age, 15-PGDH protein was found in the granules in subsets of the proximal tubules. Overall, these results support a possibility that 15-PGDH may regulate postnatal kidney development through interaction with COX-2.
Muneaki Matsuo - One of the best experts on this subject based on the ideXlab platform.
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Characterization of the Genomic Structure and Promoter of the Mouse NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase Gene ☆ ☆☆
Biochemical and biophysical research communications, 1997Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:Abstract The mouse NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) gene and its 5′-flanking region was cloned from a 129 mouse ES bacteriophage P1 genomic library. The gene contains 7 exons and 6 introns and is 11.3 kb in length. The transcription initiation site was mapped at 35 bases upstream from the ATG start codon. The nucleotide sequence of the 1.6 kb promoter region contains two TATA boxes and a number of potential regulatory elements including Sp1, CRE, GRE, AP1, AP2, NF-IL6 and estrogen receptor binding site. Studies of the promoter's activity showed that the first 400 nucleotides of 5′-flanking region efficiently drove the transcription of the luciferase reporter gene in U936 cells upon stimulation with a phorbol ester.
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characterization of the genomic structure and promoter of the mouse nad dependent 15 Hydroxyprostaglandin Dehydrogenase gene
Biochemical and Biophysical Research Communications, 1997Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:Abstract The mouse NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) gene and its 5′-flanking region was cloned from a 129 mouse ES bacteriophage P1 genomic library. The gene contains 7 exons and 6 introns and is 11.3 kb in length. The transcription initiation site was mapped at 35 bases upstream from the ATG start codon. The nucleotide sequence of the 1.6 kb promoter region contains two TATA boxes and a number of potential regulatory elements including Sp1, CRE, GRE, AP1, AP2, NF-IL6 and estrogen receptor binding site. Studies of the promoter's activity showed that the first 400 nucleotides of 5′-flanking region efficiently drove the transcription of the luciferase reporter gene in U936 cells upon stimulation with a phorbol ester.
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Cloning and expression of the cDNA for rat NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase.
Gene, 1997Co-Authors: Hongxing Zhang, Muneaki Matsuo, Charles Mark Ensor, Huiping Zhou, Hsin-hsiung TaiAbstract:Abstract The cDNA for rat NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) was cloned from an intestinal cDNA library. The sequence of this cDNA was found to be identical to that of the reverse transcription-polymerase chain reaction (RT-PCR) product obtained using rat lung RNA as a template. The cDNA contains a 798-bp open reading frame that codes for a protein of 266 amino acids (Mr 28 775) which shares 88.7% identity with the human 15-PGDH and 92.1% identity with the mouse 15-PGDH protein. The regions that are believed to be the NAD+ binding domain and the active site are conserved in the enzymes from the three different species. However, the sequence of the C-terminal 9 amino acids appears to be significantly different. The authenticity of the rat cDNA was confirmed by the expression of an enzymatically active 15-PGDH in E. coli.
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Cloning and expression of the cDNA for mouse NAD(+)-dependent 15-Hydroxyprostaglandin Dehydrogenase.
Biochimica et biophysica acta, 1996Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung TaiAbstract:The cDNA for mouse NAD+ dependent 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) was isolated from a lung cDNA library. The cDNA contains a 798 bp open reading frame that codes for a protein of 266 amino acids (Mr 28 775) which shares 87% identity with the human 15-PGDH protein. The regions that are believed to form the NAD+ binding site and the active site are conserved in the mouse and human enzymes. The authenticity of the mouse cDNA was confirmed by expression of an active 15-PGDH inEscherichia coli. Northern blot analysis demonstrated that 15-PGDH mRNA is expressed primarily in lung, intestine, stomach and liver.