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Molecular and Cellular Biochemistry

, Volume 367, Issue 1–2, pp 175–183 | Cite as

Ouabain-stimulated trafficking regulation of the Na/K-ATPase and NHE3 in renal proximal tubule cells

  • Yanling Yan
  • Steven Haller
  • Anna Shapiro
  • Nathan Malhotra
  • Jiang Tian
  • Zijian Xie
  • Deepak Malhotra
  • Joseph I. Shapiro
  • Jiang Liu
Article

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 22Na+ 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 22Na+ 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.

Keywords

Ouabain Na/K-ATPase signaling Na/K-ATPase NHE3 Redistribution 

Notes

Acknowledgments

The authors would like to thank Ms. Carol Woods her excellent help. Portions of this work were supported by National Institutes of Health Grants HL-105649 (to J.T.), HL-109015 (to Z.X. and J.I.S.) and GM-78565 (to Z.X.).

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Yanling Yan
    • 1
    • 3
  • Steven Haller
    • 1
  • Anna Shapiro
    • 1
  • Nathan Malhotra
    • 1
  • Jiang Tian
    • 1
  • Zijian Xie
    • 1
    • 2
  • Deepak Malhotra
    • 1
  • Joseph I. Shapiro
    • 1
    • 2
  • Jiang Liu
    • 1
  1. 1.Department of MedicineUniversity of Toledo College of MedicineToledoUSA
  2. 2.Department of Physiology and PharmacologyUniversity of Toledo College of MedicineToledoUSA
  3. 3.Institute of Biomedical EngineeringYanshan UniversityQinhuangdaoChina

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