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Induction of Orphan Nuclear Receptor Nurr1 Expression by the Human EP 1 Prostanoid Receptors
Author(s) -
Ji Ruyue,
Chen Xiaobo,
Regan John W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.723.2
Subject(s) - creb , orphan receptor , nuclear receptor , receptor , prostaglandin e2 receptor , microbiology and biotechnology , dopaminergic , neuron derived orphan receptor 1 , biology , chemistry , endocrinology , transcription factor , biochemistry , dopamine , gene , agonist
The EP 1 prostanoid receptor is a G‐protein coupled receptor that is activated by prostaglandin E 2 (PGE 2 ). Using gene microarray analysis, the expression of Nurr1 was found to be up‐regulated by PGE 2 in HEK cells stably expressing human EP1 receptors. Nurr1 is an orphan nuclear receptor that has been found to play an important role in the development of midbrain dopaminergic neurons. The up‐regulation of Nurr1 expression was confirmed by immunoblot analysis and could be blocked using a dominant negative mutant of the cAMP response element binding protein (CREB) and by the NF‐kappa B inhibitor, BAY11‐7082. However, PGE 2 did not stimulate intracellular cAMP formation suggesting that the PGE 2 mediated induction of Nurr1 expression by the EP1 receptor involves the activation of NF‐kappa B and CREB signaling in a cAMP independent manner. Furthermore EP 1 receptors have been reported to be expressed in the dopaminergic neurons of the rat substantial nigra. Our findings provide a basis for possible interactions between EP 1 receptors and Nurr1 in dopaminergic signaling pathways.