title: Ouabain-stimulated trafficking regulation of the Na/K-ATPase and NHE3 in renal proximal tubule cells.
abstract: We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase α1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the α1 subunit and NHE3 as well as transcellular (22)Na(+) transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig α1 was replaced by ouabain-resistant rat α1). Ouabain-induced inhibition of transcellular (22)Na(+) transport is due to an ouabain-induced redistribution of the α1 subunit and NHE3. In LLC-PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3, but has no significant effect on recycling of endocytosed α1 subunit. These data indicated that the ouabain-induced redistribution of the α1 subunit and NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase signaling influences NHE3 regulation.
authors.affiliation: Department of Medicine, University of Toledo College of Medicine, Toledo, OH 43614-2598, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yan
authors.forename: Steven
authors.initials: S
authors.lastname: Haller
authors.forename: Anna
authors.initials: A
authors.lastname: Shapiro
authors.forename: Nathan
authors.initials: N
authors.lastname: Malhotra
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D010042:Ouabain / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034421:Sus scrofa
chemical_list: D021122:Protein Subunits; C000613385:SLC9A3 protein, human; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase