Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells

Author:

Rojas J. D.,Sennoune S. R.,Maiti D.,Bakunts K.,Reuveni M.,Sanka S. C.,Martinez G. M.,Seftor E. A.,Meininger C. J.,Wu G.,Wesson D. E.,Hendrix M. J. C.,Martínez-Zaguilán R.

Abstract

Microvascular endothelial cells involved in angiogenesis are exposed to an acidic environment that is not conducive for growth and survival. These cells must exhibit a dynamic intracellular (cytosolic) pH (pHcyt) regulatory mechanism to cope with acidosis, in addition to the ubiquitous Na+/H+exchanger and HCO3-based H+-transporting systems. We hypothesize that the presence of plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) allows microvascular endothelial cells to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells, which are more migratory than macrovascular endothelial cells, express pmV-ATPases. Spectral imaging microscopy indicates a more alkaline pHcytat the leading than at the lagging edge of microvascular endothelial cells. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases the proton fluxes via pmV-ATPases and cell migration. These data suggest that pmV-ATPases are essential for pHcytregulation and cell migration in microvascular endothelial cells.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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