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FP Prostanoid Receptor Mediated Up‐regulation of Hypoxia‐Inducible Factor‐1α through Activation of Mitogen‐Activated Protein Kinase and Reactive Oxygen Species Signaling Pathways
Author(s) -
Sanchez Christopher,
Xu Wei,
Chou ChihLing,
Regan John
Publication year - 2015
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.29.1_supplement.621.13
Subject(s) - signal transduction , microbiology and biotechnology , mapk/erk pathway , downregulation and upregulation , receptor , protein kinase a , chemistry , prostanoid , kinase , biology , biochemistry , gene
The FP prostanoid receptor is in the family of G‐protein‐coupled receptors and is known to activate calcium and inositol phosphate signaling via coupling to G q . It's complementary ligand is prostaglandin‐F 2α (PGF 2α ). In human embryonic kidney (HEK) cells expressing the human FP receptor, we show that PGF 2α stimulation of the FP receptor upregulates the expression of hypoxia‐inducible factor‐1α (HIF‐1α), under normoxic conditions, by activation of the mitogen activated protein kinase (MAPK) and reactive oxygen species (ROS) signaling pathways. Co‐expression of dominant negative Nurr1 (DN‐Nurr1) diminished the PGF 2α stimulated upegulation of HIF‐1α expression. HIF‐1α is widely characterized in the literature as a tumor growth promoter and is often up‐regulated in cancer. Our findings provide a potential mechanism by which PGF 2α could‐upregulate the expression of HIF‐1α through Nurr1 activation.