Browsing by Author "O'Neal, Sara K"

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    A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.
    (Frontiers in oncology, 2018-01) Abaffy, Tatjana; Bain, James R; Muehlbauer, Michael J; Spasojevic, Ivan; Lodha, Shweta; Bruguera, Elisa; O'Neal, Sara K; Kim, So Young; Matsunami, Hiroaki
    Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this receptor. We detected that agonist 19-hydroxyandrostenedione, a product of the aromatase reaction, is endogenously produced upon receptor activation. We characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Furthermore, upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. The results of our study suggest that OR51E2 activation results in neuroendocrine trans-differentiation. These findings reveal a new role for OR51E2 and establish this G-protein coupled receptor as a novel therapeutic target in the treatment of prostate cancer.
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    Metabolic Changes with Base-Loading in CKD.
    (Clinical journal of the American Society of Nephrology : CJASN, 2018-06-22) Scialla, Julia J; Scialla, Julia J; Brown, Landon; Gurley, Susan; Corcoran, David L; Bain, James R; Muehlbauer, Michael J; O'Neal, Sara K; M O'Connell, Thomas; Wolf, Myles; Melamed, Michal L; Hostetter, Thomas H; Abramowitz, Matthew K