title: Cardiac Nitric Oxide Synthases and Na⁺/K⁺-ATPase in the Rat Model of Polycystic Ovary Syndrome Induced by Dihydrotestosterone.
abstract: Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1,177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning.
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Tepavčević
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors.forename: D V
authors.initials: DV
authors.lastname: Milutinović
authors.affiliation: Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Macut
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Stanišić
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Nikolić
authors.affiliation: Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: I
authors.initials: I
authors.lastname: Božić-Antić
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Rodaljević
authors.affiliation: CHC Bežanijska kosa, Belgrade, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Bjekić-Macut
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors.forename: G
authors.initials: G
authors.lastname: Matić
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
authors.forename: G
authors.initials: G
authors.lastname: Korićanac
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000201:enzymology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011897:Random Allocation; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D013196:Dihydrotestosterone; D013912:Threonine; D012694:Serine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C499075:Atp1a1 protein, rat; C498532:Atp1a2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase