title: Membrane androgen receptor sensitive Na+/H+ exchanger activity in prostate cancer cells.
abstract: Membrane androgen receptors (mAR) are expressed in several tumors. mAR activation by testosterone albumin conjugates (TAC) suppresses tumor growth and migration. mAR signaling involves phosphoinositide-3-kinase (PI3K) and Rho-associated protein kinase (ROCK). PI3K stimulates serum- and glucocorticoid-inducible kinase SGK1, which in turn activates Na(+)/H(+)-exchangers (NHE). In prostate cancer cells cytosolic pH (pHi) was determined utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-fluorescence and NHE-activity utilizing Na(+)-dependent cytosolic realkalinization following an ammonium pulse. TAC (100 nM) significantly increased pHi and NHE-activity, effects abrogated by NHE1-inhibitor cariporide (10 μM), SGK1-inhibitors EMD638683 (50 μM) and GSK650349 (10 μM) and ROCK-inhibitors Y-27632 (10 μM) and fasudil (100 μM). TAC treatment rapidly and significantly increased cell volume and actin polymerization, effects abolished in the presence of cariporide. Thus, mAR-activation activates cariporide-sensitive Na(+)/H(+)-exchangers, an effect requiring SGK1 and ROCK activity.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Soumya
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Pouli
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.affiliation: Department of Biochemistry, University of Crete Medical School, Heraklion, Greece; Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saad
authors.initials: S
authors.lastname: Alkahtani
authors.affiliation: Department of Physiology, University of Tübingen, Germany; Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Stournaras
authors.affiliation: Department of Physiology, University of Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000577:Amides / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D048429:Cell Size; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011944:Receptors, Androgen / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000577:Amides; D001549:Benzamides; D001565:Benzoates; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006146:Guanidines; D006834:Hydrazines; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D011944:Receptors, Androgen; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D054460:rho-Associated Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C569030:EMD 638683; C108830:Y 27632; C532254:2-cyclopentyl-4-(5-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl)-benzoic acid; C093373:cariporide
keywords: Actin; Cytosolic pH; EMD638683; Na(+)/H(+) exchanger; ROCK; SGK1; Y-27632