A5047414438- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Protein Kinase Regulation and GTPase Signaling
- Eicosanoids and Hypertension Pharmacology
- Adipose Tissue and Metabolism
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Pharmacogenetics and Drug Metabolism
- Nitric Oxide and Endothelin Effects
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Trace Elements in Health
- Venomous Animal Envenomation and Studies
- Cancer, Lipids, and Metabolism
- Helicobacter pylori-related gastroenterology studies
- Redox biology and oxidative stress
- Metabolomics and Mass Spectrometry Studies
- Prostate Cancer Treatment and Research
- Heavy Metal Exposure and Toxicity
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- Hormonal and reproductive studies
- Metabolism, Diabetes, and Cancer
Showa University
2015-2024
Government of Western Australia Department of Health
2010
Kitasato University
1999-2009
Showa Pharmaceutical University
2009
Nippon Medical School
2005
National Institute of Infectious Diseases
2005
National Cerebral and Cardiovascular Center
1994-2002
Fukuoka University
1997
Kyushu University
1995-1997
University College London
1997
There exist two distinct isozymes of prostaglandin-endoperoxide synthase (PES). PES-2 mRNA is synergistically induced by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in bovine arterial endothelial cells. On the other hand, PES-1 constitutively expressed under these conditions. Therefore, promoter activities human genes for −2 cells were examined. The 5′-flanking region gene (nucleotides −327 to +59) showed activity inducible LPS TPA using transient transfection...
The human gene ( PTGS2 ) encoding an inducible isozyme of prostaglandin‐endoperoxide synthase (prostaglandin‐endoperoxide 2) that is distinct from the well‐characterized and constitutive 1), was isolated using a polymerase‐chain reaction‐generated cDNA fragment probe for 2. Nucleotide sequence analysis entire prostaglandin‐endoperoxide‐synthase‐2 demonstrated it more than 8.3 kb in size consists ten exons; this very similar to murine chicken genes. structures exons were also those...
Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death considered to be the critical event in APAP-induced hepatotoxicity, underlying mechanism remains unclear. Ferroptosis newly discovered type that caused by loss cellular redox homeostasis. As glutathione (GSH) depletion triggers we investigated role ferroptosis murine model hepatotoxicity (evaluated terms ALT, AST, and histopathological score), lipid peroxidation (4-HNE MDA),...
Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor protein is cause familial VHL disease and sporadic kidney cancer. The gene product (pVHL) a component an E3 ubiquitin ligase complex that targets hypoxia-inducible factor (HIF) 1 2 alpha subunits for polyubiquitylation. This process dependent on hydroxylation conserved proline residues HIF-1/2 in presence oxygen. In our effort to identify orphan HIF-like proteins data base are potential pVHL complex, we report multiple...
Abstract Thioredoxin reductase (TrxR) is a selenoprotein that catalyzes the reduction of active site disulfide thioredoxin (Trx), which regulates redox status cells. In present study, we found TrxR1, one three TrxR isozymes, was induced by cadmium as well tumor necrosis factor α (TNFα) in bovine arterial endothelial cells (BAEC), and investigated mechanism cadmium‐induced TrxR1 expression. We here showed cadmium, differently from TNFα, enhanced promoter activity 5′‐flanking region human gene...
The promoter activity of 1432 bp upstream the human prostaglandin‐endoperoxide synthase 2 gene ( PTGS2 ) was examined in differentiated U937 monocytic cells expressing mRNA. Transient transfection experiments were performed using these and reporter vectors containing region with deletions or site‐specific mutations luciferase gene. deletion destruction cyclic AMP response element (nucleotides −59 to −53) markedly reduced this Electrophoretic mobility shift assays showed that a nuclear...
A universal response to changes in cellular oxygen tension is governed by a family of heterodimeric transcription factors called hypoxia-inducible factor (HIF). Tumor hypoxia, as well various cancer-causing mutations, has been shown elevate the level HIF-1alpha, signifying critical role HIF pathway cancer development. The recently identified third member human HIF-alpha family, HIF-3alpha, produces multiple splice variants that contain extra DNA binding elements and protein-protein...
Extracellular phospholipase A2 was purified about 1.7 × 105 fold to near homogeneity from human synovial fluid of rheumatoid arthritis by sequential use column chromatographies on heparin-Sepharose, butyl-Toyopearl, and reversed-phase HPLC. The final preparation showed a single band SDS-polyacrylamide gel electrophoresis, its molecular mass estimated be approximately 13, 700 daltons. enzyme had pH optimum 9.0 required Ca2+ for maximum activity. It hydrolyzed phosphatidylethanolamine more...
Resolution of inflammation is an active process that mediated in part by antiinflammatory lipid mediators. Although phospholipase A2 (PLA2) enzymes have been implicated the promotion through mobilizing mediators, molecular entity PLA2 subtypes acting upstream mediators remains unknown. Herein, we show secreted group IID (PLA2G2D) preferentially expressed CD11c+ dendritic cells (DCs) and macrophages displays a pro-resolving function. In hapten-induced contact dermatitis, resolution, not...
Choline supplies methyl groups for regeneration of methionine and the donor S-adenosylmethionine in liver. Here, we report that catabolism membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored hepatic PC to be utilized metabolism. PNPLA7-deficient mice show marked decreases GPC, choline, several metabolites related cycle, accompanied various signs insufficiency, including growth...
Among the many mammalian secreted phospholipase A2 (sPLA2) enzymes, PLA2G3 (group III A2) is unique in that it possesses unusual N- and C-terminal domains its central sPLA2 domain homologous to bee venom PLA2 rather than other sPLA2s. To elucidate vivo actions of this atypical sPLA2, we generated transgenic (Tg) mice overexpressing human PLA2G3. Despite marked increases activity mature 18-kDa protein circulation tissues, Tg displayed no apparent abnormality up 9 months age. However,...
Prostacyclin synthase catalyzes the conversion of prostaglandin H, to prostacyclin, which is a powerful vasodilator and most potent natural occurring inhibitor platelet aggregation.In present study, we determined amino acid sequence bovine prostacyclin by combined protein chemical molecular cloning techniques.The enzyme was purified characterized from aorta microsomes, partial sequences were with native endoproteinase Lys-C-cleaved peptides.Using primers synthesized according sequences, cDNA...
Although lipid metabolism is thought to be important for the proper maturation and function of spermatozoa, molecular mechanisms that underlie this dynamic process in gonads remains incompletely understood. Here, we show group III phospholipase A2 (sPLA2-III), a member secreted (sPLA2) family, expressed mouse proximal epididymal epithelium targeted disruption gene encoding protein (Pla2g3) leads defects sperm fertility. testicular spermatogenesis Pla2g3-/- mice was grossly normal,...
mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme that functions downstream of COX (cyclo-oxygenase)-2 in the PGE2 (prostaglandin E2)-biosynthesis pathway. Although COX-2-derived known to play role development various tumours, involvement carcinogenesis has not yet been fully understood. In present study, we used LLC (Lewis lung carcinoma) cells with knockdown or overexpression, as well mPGES-1-deficient mice examine roles cancer cell- and host-associated...
Ejaculated mammalian sperm must undergo a maturation process called capacitation before they are able to fertilize an egg. Several studies have suggested role for members of the secreted phospholipase A2 (sPLA2) family in capacitation, acrosome reaction (AR), and fertilization, but molecular nature these enzymes their specific roles remained elusive. Here, we demonstrated that mouse group X sPLA2 (mGX) is major enzyme present spermatozoa it released active form during through spontaneous AR....