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Am J Physiol Heart Circ Physiol (May 5, 2006). doi:10.1152/ajpheart.00166.2006
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Submitted on February 14, 2006
Accepted on March 24, 2006

Vacuolar Type H+-ATPases at the Plasma Membrane Regulate pH and Cell Migration in Microvascular Endothelial Cells

Jose D Rojas1, Souad R Sennoune1, Debasish Maiti1, Karina Bakunts1, Moshe Reuveni2, Shankar C Sanka1, Gloria M Martinez1, Elisabeth A Seftor3, Cynthia J. Meininger4, Donald E. Wesson1, Mary JC Hendrix3, Raul Martinez-Zaguilan1*, and Guoyao Wu5

1 Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
2 Ornamental Horticulture, ARO Volcani Center, Bet-Dagan, Israel
3 Pediatrics, Childern's Memorial Research Cente, Northwestern University School of Mediciner, Chicago, Illinois, United States
4 Department of Medical Physiology, Health Science Center, Texas A and M University, College Station, Texas, United States
5 Animal Science, Texas A&M University, College Station, Texas, United States

* To whom correspondence should be addressed. E-mail: raul.martinezzaguilan{at}ttuhsc.edu.

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 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 microvascular endothelial cells exhibit plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells that are more migratory than macrovascular endothelial cells express pmV-ATPases. Spectral imaging microscopy indicates that the leading edge of microvascular endothelial cells exhibits a more alkaline pHcyt than the lagging edge. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases both 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.




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