Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2

Autor: Sachiko Oh-ishi, Fumiaki Kojima, Yoshihito Nakatani, Ichiro Kudo, Hiroaki Naraba, Toshihiro Tanioka, Akinori Ueno, Makoto Murakami, Natsuki Semmyo, Mai Fueki, Tomomi Ikeda
Rok vydání: 2000
Předmět:
musculoskeletal diseases
Molecular Sequence Data
Prostaglandin
Prostaglandin E synthase
Biochemistry
Dinoprostone
Proinflammatory cytokine
Rats
Sprague-Dawley
chemistry.chemical_compound
Mice
Phospholipase A2
Microsomes
medicine
Animals
Humans
Amino Acid Sequence
Prostaglandin E2
education
Molecular Biology
Glutathione Transferase
Prostaglandin-E Synthases
education.field_of_study
Osteoblasts
biology
Sequence Homology
Amino Acid
Macrophages
Prostaglandin E synthase 2
Cell Membrane
Membrane Proteins
Cell Biology
Recombinant Proteins
Cell biology
Rats
Intramolecular Oxidoreductases
Isoenzymes
Kinetics
chemistry
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
biology.protein
Mutagenesis
Site-Directed
lipids (amino acids
peptides
and proteins)
Arachidonic acid
Cyclooxygenase
Rabbits
Sequence Alignment
medicine.drug
Zdroj: The Journal of biological chemistry. 275(42)
ISSN: 0021-9258
Popis: Here we report the molecular identification of membrane-bound glutathione (GSH)-dependent prostaglandin (PG) E(2) synthase (mPGES), a terminal enzyme of the cyclooxygenase (COX)-2-mediated PGE(2) biosynthetic pathway. The activity of mPGES was increased markedly in macrophages and osteoblasts following proinflammatory stimuli. cDNA for mouse and rat mPGESs encoded functional proteins that showed high homology with the human ortholog (microsomal glutathione S-transferase-like 1). mPGES expression was markedly induced by proinflammatory stimuli in various tissues and cells and was down-regulated by dexamethasone, accompanied by changes in COX-2 expression and delayed PGE(2) generation. Arg(110), a residue well conserved in the microsomal GSH S-transferase family, was essential for catalytic function. mPGES was functionally coupled with COX-2 in marked preference to COX-1, particularly when the supply of arachidonic acid was limited. Increased supply of arachidonic acid by explosive activation of cytosolic phospholipase A(2) allowed mPGES to be coupled with COX-1. mPGES colocalized with both COX isozymes in the perinuclear envelope. Moreover, cells stably cotransfected with COX-2 and mPGES grew faster, were highly aggregated, and exhibited aberrant morphology. Thus, COX-2 and mPGES are essential components for delayed PGE(2) biosynthesis, which may be linked to inflammation, fever, osteogenesis, and even cancer.
Databáze: OpenAIRE
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