Abstract |
Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived prostaglandin (PG) H(2) to PGE(2), occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein belonging to the MAPEG (for membrane-associated proteins involved in eicosanoid and GSH metabolism) family. This enzyme is markedly induced by proinflammatory stimuli, is down-regulated by anti-inflammatory glucocorticoids, and is functionally coupled with cyclooxygenase (COX)-2 in marked preference to COX-1. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate PGE(2) production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes. In particular, recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti- cancer drugs.
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Authors | Makoto Murakami, Ichiro Kudo |
Journal | Current pharmaceutical design
(Curr Pharm Des)
Vol. 12
Issue 8
Pg. 943-54
( 2006)
ISSN: 1381-6128 [Print] United Arab Emirates |
PMID | 16533161
(Publication Type: Journal Article, Review)
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Chemical References |
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Enzyme Inhibitors
- Isoenzymes
- Prostaglandin-Endoperoxide Synthases
- Intramolecular Oxidoreductases
- PTGES protein, human
- PTGES2 protein, human
- Prostaglandin-E Synthases
- Dinoprostone
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Topics |
- Amino Acid Sequence
- Animals
- Anti-Inflammatory Agents
(pharmacology, therapeutic use)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Arthritis, Rheumatoid
(drug therapy, metabolism)
- Colorectal Neoplasms
(drug therapy, metabolism)
- Dinoprostone
(metabolism)
- Drug Delivery Systems
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Humans
- Intramolecular Oxidoreductases
(antagonists & inhibitors, genetics, metabolism)
- Isoenzymes
(antagonists & inhibitors, genetics, metabolism)
- Molecular Sequence Data
- Pain
(drug therapy, metabolism)
- Prostaglandin-E Synthases
- Prostaglandin-Endoperoxide Synthases
(metabolism)
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