Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells.
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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 pHcyt at 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 pHcyt regulation and cell migration in microvascular endothelial cells.
Am J Physiol Heart Circ Physiol
author list (cited authors)
Rojas, J. D., Sennoune, S. R., Maiti, D., Bakunts, K., Reuveni, M., Sanka, S. C., ... Martnez-Zaguiln, R.
complete list of authors
Rojas, JD||Sennoune, SR||Maiti, D||Bakunts, K||Reuveni, M||Sanka, SC||Martinez, GM||Seftor, EA||Meininger, CJ||Wu, G||Wesson, DE||Hendrix, MJC||Martínez-Zaguilán, R