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The Nurr1 transcription factor is upregulated by the EP1 prostanoid receptor in monomethylarsonous acid treated UROtsa cells
Author(s) -
Sanchez Christopher M.,
Gandolfi A. Jay,
Regan John W.
Publication year - 2012
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.26.1_supplement.663.7
Subject(s) - downregulation and upregulation , prostaglandin e2 receptor , receptor , prostanoid , nuclear receptor , chemistry , transcription factor , pharmacology , microbiology and biotechnology , biology , biochemistry , agonist , gene
Monomethylarsonous acid (MMA(III)) is a toxic metabolite of arsenic that has been used to study the urothelial effects of arsenicals. A previous study has shown that acute treatment of immortalized UROtsa bladder cells with MMA(III) activate cyclooxygenase 2, which along with cyclooxygenase 1, is required for prostaglandin synthesis. Prostaglandins act on receptors that are members of the G‐protein coupled receptors family responsible for regulating pain, fever, and inflammation and are involved in such cellular processes as proliferation, migration, and apoptosis. Recently, we have shown that stimulation of the EP1 prostanoid receptor by prostaglandin E2 upregulates expression of the orphan nuclear receptor Nurr1. Nurr1 is a transcription factor that is essential for the development and maintenance of midbrain dopaminergic neurons and has been shown to regulate both cell survival and death. In the current study, we examined the potential role of prostanoid receptors in the regulation of Nurr1 expression in UROtsa cells. Treatment of UROtsa cells with MMA(III) resulted in a 3‐fold upregulation of Nurr1 protein expression after 1 hour that was sustained for up to 12 hours. Pretreatment of UROtsa cells with SC‐51322, a selective EP1 receptor antagonist, inhibited the upregulation of Nurr1 expression by MMA(III), suggesting involvement of the EP1 prostanoid receptor with the upregulation of Nurr1 by MMA(III).