Intracellular-specific colocalization of prostaglandin E2 synthases and cyclooxygenases in the brain.

Authors: Vazquez-Tello, A  Fan, L  Hou, X  Joyal, JS  Mancini, JA  Quiniou, C  Clyman, RI  Gobeil F, JR  Varma, DR  Chemtob, S 
Citation: Vazquez-Tello A, etal., Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1155-63. Epub 2004 Jul 29.
Pubmed: (View Article at PubMed) PMID:15284079
DOI: Full-text: DOI:10.1152/ajpregu.00077.2004

Prostaglandin E2 (PGE2) is the major primary prostaglandin generated by brain cells. However, the coordination and intracellular localization of the cyclooxygenases (COXs) and prostaglandin E synthases (PGESs) that convert arachidonic acid to PGE2 in brain tissue are not known. We aimed to determine whether microsomal and cytosolic PGES (mPGES-1 and cPGES) colocalize and coordinate activity with either COX-1 or COX-2 in brain tissue, particularly during development. Importantly, we found that cytosolic PGES also associates with microsomes (cPGES-m) from the cerebrum and cerebral vasculature of the pig and rat as well as microsomes from various cell lines; this seemed dependent on the carboxyl terminal 35-amino acid domain and a cysteine residue (C58) of cPGES. In microsomal membranes from the postnatal brain and cerebral microvessels of mature animals, cPGES-m colocalized with both COX-1 and COX-2, whereas mPGES-1 was undetectable in these microsomes. Accordingly, in this cell compartment, cPGES could coordinate its activity with COX-2 and COX-1 (partly inhibited by NS398); albeit in microsomes of the brain microvasculature from newborns, mPGES-1 was also present. In contrast, in nuclei of brain parenchymal and endothelial cells, mPGES-1 and cPGES colocalized exclusively with COX-2 (determined by immunoblotting and immunohistochemistry); these PGESs contributed to conversion of PGH2 into PGE2. Hence, contrary to a previously proposed model of exclusive COX-2/mPGES-1 coordination, COX-2 can coordinate with mPGES-1 and/or cPGES in the brain, depending on the cell compartment and the age group.

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RGD Object Information
RGD ID: 2300105
Created: 2008-09-04
Species: All species
Last Modified: 2008-09-04
Status: ACTIVE