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Low concentrations of ouabain induce vascular smooth muscle cell proliferation
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Ouabain is a well known inhibitor of the Na+ pump in all mammalian cells. We have demonstrated that ouabain at concentrations below those which inhibit the pump, i.e. 0.1 nM and 1.0 nM, induce proliferation of saphenous vein smooth muscle cells as measured by bromodeoxyuridine (BrdU) uptake. Ouabain at these low concentrations also activated MAPK. Proliferating concentrations of the drug did not increase levels of Ca(i)2+, suggesting no effect of this ion in the process. In addition, incubation of the cells in low levels of K+, which has been shown to inhibit the pump, had no effect on proliferation. These data show that low concentrations of ouabain that do not inhibit the Na+ pump can activate proliferation of vascular smooth muscle cells, suggesting that the pump complex may act as a transducing receptor.
Insights
Low concentrations of ouabain, a sodium-potassium pump inhibitor, stimulate saphenous vein smooth muscle cell proliferation and activate MAPK without affecting calcium levels. This suggests a non-inhibitory role for the pump in cell signaling.
Area of Science:
- Cardiovascular Biology
- Cell Signaling
- Pharmacology
Background:
- Ouabain is a known inhibitor of the sodium-potassium (Na+/K+-ATPase) pump in mammalian cells.
- The Na+/K+-ATPase pump plays critical roles in maintaining cellular ion gradients and membrane potential.
Purpose of the Study:
- To investigate the effects of low-concentration ouabain on vascular smooth muscle cell proliferation.
- To determine the signaling pathways involved in ouabain-induced cell proliferation.
Main Methods:
- Saphenous vein smooth muscle cells were treated with low concentrations of ouabain (0.1 nM and 1.0 nM).
- Cell proliferation was assessed using bromodeoxyuridine (BrdU) uptake.
- Mitogen-activated protein kinase (MAPK) activation and intracellular calcium levels (Ca(i)2+) were measured.
- Cells were also incubated in low potassium (K+) conditions to assess pump inhibition effects.
Main Results:
- Low concentrations of ouabain (0.1 nM and 1.0 nM) significantly induced proliferation of saphenous vein smooth muscle cells.
- Ouabain at these concentrations activated MAPK signaling.
- No increase in intracellular calcium levels was observed, indicating calcium's non-involvement.
- Low K+ levels, which inhibit the Na+/K+-ATPase pump, did not affect cell proliferation.
Conclusions:
- Low-dose ouabain can activate vascular smooth muscle cell proliferation independently of Na+/K+-ATPase pump inhibition.
- The Na+/K+-ATPase pump complex may function as a receptor, transducing signals that promote cell proliferation.
- MAPK activation is involved in the proliferative response induced by non-inhibitory ouabain concentrations.