15 Hydroxyprostaglandin Dehydrogenase - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

15 Hydroxyprostaglandin Dehydrogenase

The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform

15 Hydroxyprostaglandin Dehydrogenase – Free Register to Access Experts & Abstracts

Hsin-hsiung Tai – One of the best experts on this subject based on the ideXlab platform.

  • Synthesis and biological evaluation of novel thiazolidinedione analogues as 15Hydroxyprostaglandin Dehydrogenase inhibitors.
    Journal of medicinal chemistry, 2011
    Co-Authors: Sandeep Karna, Cheol Hee Choi, Min Tong, Hsin-hsiung Tai, Chul Ho Jang, Hoon Cho
    Abstract:

    Novel thiazolidinedione analogues as 15Hydroxyprostaglandin 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.

  • 15Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Gastric Cancer
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2009
    Co-Authors: Alexandra Thiel, Hsin-hsiung Tai, Aparna Ganesan, Johanna Mrena, Siina Junnila, Antti I. Nykänen, Annabrita Hemmes, Outi Monni, Arto Kokkola, Caj Haglund
    Abstract:

    Purpose: We have investigated the expression and regulation of 15Hydroxyprostaglandin 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.

  • nonsteroidal anti inflammatory drugs suppress glioma via 15 Hydroxyprostaglandin Dehydrogenase
    Cancer Research, 2008
    Co-Authors: Naoki Wakimoto, Hsin-hsiung Tai, Ido Wolf, Dong Yin, James Okelly, Tadayuki Akagi, Lilach Abramovitz, Keith L Black, Phillip H Koeffler
    Abstract:

    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 15Hydroxyprostaglandin 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.

Charles Mark Ensor – One of the best experts on this subject based on the ideXlab platform.

J R Challis – One of the best experts on this subject based on the ideXlab platform.

Tianxin Yang – One of the best experts on this subject based on the ideXlab platform.

  • Postnatal regulation of 15Hydroxyprostaglandin Dehydrogenase in the rat kidney
    American journal of physiology. Renal physiology, 2014
    Co-Authors: Ying Liu, Zhanjun Jia, Ying Sun, Li Zhou, Maicy Downton, Ren Chen, Aihua Zhang, Tianxin Yang
    Abstract:

    Cyclooxygenase 2 (COX-2) has an established role in postnatal kidney development. 15Hydroxyprostaglandin 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.

  • Characterization of the Genomic Structure and Promoter of the Mouse NAD+-Dependent 15Hydroxyprostaglandin Dehydrogenase Gene ☆ ☆☆
    Biochemical and biophysical research communications, 1997
    Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung Tai
    Abstract:

    Abstract The mouse NAD+-dependent 15Hydroxyprostaglandin 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.

  • characterization of the genomic structure and promoter of the mouse nad dependent 15 Hydroxyprostaglandin Dehydrogenase gene
    Biochemical and Biophysical Research Communications, 1997
    Co-Authors: Muneaki Matsuo, Charles Mark Ensor, Hsin-hsiung Tai
    Abstract:

    Abstract The mouse NAD+-dependent 15Hydroxyprostaglandin 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.

  • Cloning and expression of the cDNA for rat NAD+-dependent 15Hydroxyprostaglandin Dehydrogenase.
    Gene, 1997
    Co-Authors: Hongxing Zhang, Muneaki Matsuo, Charles Mark Ensor, Huiping Zhou, Hsin-hsiung Tai
    Abstract:

    Abstract The cDNA for rat NAD+-dependent 15Hydroxyprostaglandin 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.