| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Pharmacology
2 and Medicine, Medical College of Ohio, Toledo, OH 43614
Foxglove (Digitalis purpurea), from which the cardiac glycoside compounds digitalis and digitonin are derived.
The Na+-K+-ATPase, or Na+ pump, is a member of the P-type ATPase superfamily. In addition to pumping ions, Na+-K+-ATPase is engaged in assembly of multiple protein complexes that transmit signals to different intracellular compartments. The signaling function of the enzyme appears to have been acquired through the evolutionary incorporation of many specific binding motifs that interact with proteins and ligands. In some cell types the signaling Na+--ATPase and its protein partners are compartmentalized in coated pits (i.e., caveolae) the plasma membrane. Binding of ouabain to the signaling Na+-K+-ATPase activates the cytoplasmic tyrosine kinase Src, resulting in the formation of an active "binary receptor" that phosphorylates and assembles other proteins into different signaling modules. This in turn activates multiple protein kinase cascades including mitogen-activated protein kinases and protein kinase C isozymes in a cell-specific manner. It also increases mitochondrial production of reactive oxygen species (ROS)and regulates intracellular calcium concentration. Crosstalk among the activated pathways eventually results in changes in the expression of a number of genes. Although ouabain stimulates hypertrophic growth in cardiac myocytes and proliferation in smooth muscle cells, it also induces apoptosis in many malignant cells. Finally, the signaling function of the enzyme is also pivotal to ouabain-induced nongenomic effects on cardiac myocytes.
This article has been cited by other articles:
|
|
 |
|
  Y. Bao, L. M. Weiss, M. Hashimoto, T. Nara, and H. Huang Protein Kinase A Regulatory Subunit Interacts with P-Type ATPases in Trypanosoma cruzi Am J Trop Med Hyg, June 1, 2009; 80(6): 941 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tian, X. Li, M. Liang, L. Liu, J. X. Xie, Q. Ye, P. Kometiani, M. Tillekeratne, R. Jin, and Z. Xie Changes in Sodium Pump Expression Dictate the Effects of Ouabain on Cell Growth J. Biol. Chem., May 29, 2009; 284(22): 14921 - 14929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cao, K. Payne, W. Lee-Kwon, Z. Zhang, S. W. Lim, J. Hamlyn, M. P. Blaustein, H. M. Kwon, and T. L. Pallone Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat Am J Physiol Renal Physiol, January 1, 2009; 296(1): F98 - F106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cai, H. Wang, Y. Chen, L. Liu, W. T Gunning, L. E. M. Quintas, and Z.-J. Xie Regulation of caveolin-1 membrane trafficking by the Na/K-ATPase J. Cell Biol., September 22, 2008; 182(6): 1153 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, Z. Spicarova, S. Rydholm, J. Li, H. Brismar, and A. Aperia Ankyrin B Modulates the Function of Na,K-ATPase/Inositol 1,4,5-Trisphosphate Receptor Signaling Microdomain J. Biol. Chem., April 25, 2008; 283(17): 11461 - 11468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Pierre, Y. Sottejeau, J.-M. Gourbeau, G. Sanchez, A. Shidyak, and G. Blanco Isoform specificity of Na-K-ATPase-mediated ouabain signaling Am J Physiol Renal Physiol, April 1, 2008; 294(4): F859 - F866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhang, C. Cao, Z. Zhang, W. G. Wier, A. Edwards, and T. L. Pallone Membrane current oscillations in descending vasa recta pericytes Am J Physiol Renal Physiol, March 1, 2008; 294(3): F656 - F666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Newman, P. Yang, A. D. Pawlus, and K. I. Block Cardiac Glycosides as Novel Cancer Therapeutic Agents Mol. Interv., February 1, 2008; 8(1): 36 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D.T. Costa, S. V. Pierre, M. V. Cohen, J. M. Downey, and K. D. Garlid cGMP signalling in pre- and post-conditioning: the role of mitochondria Cardiovasc Res, January 15, 2008; 77(2): 344 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Stahli, A. Breitenstein, A. Akhmedov, G. G. Camici, K. Shojaati, N. Bogdanov, J. Steffel, D. Ringli, T. F. Luscher, and F. C. Tanner Cardiac Glycosides Regulate Endothelial Tissue Factor Expression in Culture Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2769 - 2776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Richards, K. Bommert, G. Szabo, and R. Miles Differential expression of Na+/K+-ATPase {alpha}-subunits in mouse hippocampal interneurones and pyramidal cells J. Physiol., December 1, 2007; 585(2): 491 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Ouabain modulation of cellular calcium stores and signaling Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1518 - F1532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kimura, P. B. Allen, A. C. Nairn, and M. J. Caplan Arrestins and Spinophilin Competitively Regulate Na+,K+-ATPase Trafficking through Association with a Large Cytoplasmic Loop of the Na+,K+-ATPase Mol. Biol. Cell, November 1, 2007; 18(11): 4508 - 4518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Khundmiri, V. Amin, J. Henson, J. Lewis, M. Ameen, M. J. Rane, and N. A. Delamere Ouabain stimulates protein kinase B (Akt) phosphorylation in opossum kidney proximal tubule cells through an ERK-dependent pathway Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1171 - C1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Schoner and G. Scheiner-Bobis Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth Am J Physiol Cell Physiol, August 1, 2007; 293(2): C509 - C536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Modification of cytosolic calcium signaling by subplasmalemmal microdomains Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1827 - F1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pasdois, C. L. Quinlan, A. Rissa, L. Tariosse, B. Vinassa, A. D. T. Costa, S. V. Pierre, P. Dos Santos, and K. D. Garlid Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1470 - H1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Pierre, C. Yang, Z. Yuan, J. Seminerio, C. Mouas, K. D. Garlid, P. Dos-Santos, and Z. Xie Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts Cardiovasc Res, February 1, 2007; 73(3): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.M. Payne, C. Weber, C. Crowley-Skillicorn, K. Dvorak, H. Bernstein, C. Bernstein, H. Holubec, B. Dvorakova, and H. Garewal Deoxycholate induces mitochondrial oxidative stress and activates NF-{kappa}B through multiple mechanisms in HCT-116 colon epithelial cells Carcinogenesis, January 1, 2007; 28(1): 215 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-N. T. Nguyen, D. P. Wallace, and G. Blanco Ouabain Binds with High Affinity to the Na,K-ATPase in Human Polycystic Kidney Cells and Induces Extracellular Signal-Regulated Kinase Activation and Cell Proliferation J. Am. Soc. Nephrol., January 1, 2007; 18(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. V. Wattenberg Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis Am J Physiol Cell Physiol, January 1, 2007; 292(1): C24 - C32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Khundmiri, M. A. Metzler, M. Ameen, V. Amin, M. J. Rane, and N. A. Delamere Ouabain induces cell proliferation through calcium-dependent phosphorylation of Akt (protein kinase B) in opossum kidney proximal tubule cells Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1247 - C1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pittner, K. Rhinehart, and T. L. Pallone Ouabain modulation of endothelial calcium signaling in descending vasa recta Am J Physiol Renal Physiol, October 1, 2006; 291(4): F761 - F769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Buckner, S. Wilson, S. Kurk, M. Hardy, N. Miessner, and M. A. Jutila Use of Early Passage Fetal Intestinal Epithelial Cells in Semi-High-Throughput Screening Assays: An Approach to Identify New Innate Immune System Adjuvants J Biomol Screen, September 1, 2006; 11(6): 664 - 671. [Abstract] [PDF]
|
|
|
|
|
|
S. Zhang, S. Malmersjo, J. Li, H. Ando, O. Aizman, P. Uhlen, K. Mikoshiba, and A. Aperia Distinct Role of the N-terminal Tail of the Na,K-ATPase Catalytic Subunit as a Signal Transducer J. Biol. Chem., August 4, 2006; 281(31): 21954 - 21962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Kotova, L. Al-Khalili, S. Talia, C. Hooke, O. V. Fedorova, A. Y. Bagrov, and A. V. Chibalin Cardiotonic Steroids Stimulate Glycogen Synthesis in Human Skeletal Muscle Cells via a Src- and ERK1/2-dependent Mechanism J. Biol. Chem., July 21, 2006; 281(29): 20085 - 20094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. T. Wang, S. Portbury, M. B. Thomas, S. Barney, D. J. Ricca, D. L. Morris, D. S. Warner, and D. C. Lo Cardiac glycosides provide neuroprotection against ischemic stroke: Discovery by a brain slice-based compound screening platform PNAS, July 5, 2006; 103(27): 10461 - 10466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, S. Zelenin, A. Aperia, and O. Aizman Low Doses of Ouabain Protect from Serum Deprivation-Triggered Apoptosis and Stimulate Kidney Cell Proliferation via Activation of NF-{kappa}B J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1848 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Korovkina, A. M. Brainard, and S. K. England Translocation of an endoproteolytically cleaved maxi-K channel isoform: mechanisms to induce human myometrial cell repolarization J. Physiol., June 1, 2006; 573(2): 329 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Silva, A. I. Duarte, A. C. Rego, C. R. Oliveira, and P. P. Goncalves Effect of Chronic Exposure to Aluminium on Isoform Expression and Activity of Rat (Na+/K+)ATPase Toxicol. Sci., December 1, 2005; 88(2): 485 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom and G. L. Aistrup Digitalis: new actions for an old drug Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1781 - H1793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yuan, T. Cai, J. Tian, A. V. Ivanov, D. R. Giovannucci, and Z. Xie Na/K-ATPase Tethers Phospholipase C and IP3 Receptor into a Calcium-regulatory Complex Mol. Biol. Cell, September 1, 2005; 16(9): 4034 - 4045. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ASPET Journals | Pharmacological Reviews | Drug Metabolism and Disposition |
| Molecular Interventions | Molecular Pharmacology | J Pharmacology and Exp Therapeutics |
