Plasmalemmal vacuolar H+-ATPase is decreased in microvascular endothelial cells from a diabetic model

Jose D. Rojas, Souad R. Sennoune, Gloria M. Martinez, Karina Bakunts, Cynthia J. Meininger, Guoyao Wu, Donald E. Wesson, Elisabeth A. Seftor, Mary J.C. Hendrix, Raul Martínez-Zaguilán

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Angiogenesis requires invasion of extracellular matrix (ECM) proteins by endothelial cells and occurs in hypoxic and acidic environments that are not conducive for cell growth and survival. We hypothesize that angiogenic cells must exhibit a unique system to regulate their cytosolic pH in order to cope with these harsh conditions. The plasmalemmal vacuolar type H+-ATPase (pmV-ATPase) is used by cells exhibiting an invasive phenotype. Because angiogenesis is impaired in diabetes, we hypothesized that pmV-ATPase is decreased in microvascular endothelial cells from diabetic rats. The in vitro angiogenesis assays demonstrated that endothelial cells were unable to form capillary-like structures in diabetes. The proton fluxes were slower in cells from diabetic than normal model, regardless of the presence or absence of Na+ and HCO3- and were suppressed by V-H +-ATPase inhibitors. Immunocytochemical data revealed that pmV-ATPases were inconspicuous at the plasma membrane of cells from diabetic whereas in normal cells were prominent. The pmV-ATPase activity was lower in cells from diabetic than normal models. Inhibition of V-H+-ATPase suppresses invasion/migration of normal cells, but have minor effects in cells from diabetic models. These novel observations suggest that the angiogenic abnormalities in diabetes involve a decrease in pmV-ATPase in microvascular endothelial cells.

Original languageEnglish (US)
Pages (from-to)190-200
Number of pages11
JournalJournal of Cellular Physiology
Volume201
Issue number2
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Rojas, J. D., Sennoune, S. R., Martinez, G. M., Bakunts, K., Meininger, C. J., Wu, G., Wesson, D. E., Seftor, E. A., Hendrix, M. J. C., & Martínez-Zaguilán, R. (2004). Plasmalemmal vacuolar H+-ATPase is decreased in microvascular endothelial cells from a diabetic model. Journal of Cellular Physiology, 201(2), 190-200. https://doi.org/10.1002/jcp.20059