Oxygen modulates the release of urokinase and plasminogen activator inhibitor-1 by retinal pigment epithelial cells

Jonathan T. Erichsen, John Jarvis-Evans, Asud Khaliq, Mike Boulton

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The aims of this study were to examine the effect of oxygen, in the presence or absence of exogenous growth factors, on the release of plasminogen activators and plasminogen activator inhibitor-1 by cultured human retinal pigment epithelial cells. Antigen and activity levels of urokinase, tissue plasminogen activator and plasminogen activator inhibitor were measured in conditioned media after cells were exposed to three different oxygen environments: hypoxia, normoxia and hyperoxia. Overall proteolytic balance was determined by zymography. The effects of exogenous basic fibroblast growth factor and transforming growth factor-beta were also examined. it was found that retinal pigment epithelial cells released urokinase, tissue plasminogen activator and plasminogen activator inhibitor in measurable quantities. After 48 h, urokinase levels were highest at normoxia, reaching 7.2ng/106 cells ( ± 2.0 SEM), whereas plasminogen activator inhibitor 1 levels were highest at hyperoxia, reaching 67.5ng/106 cells ( ± 3.7 SEM). Tissue plasminogen activator levels were minimal ( < 0.5ng/106 cells) and unaffected by both oxygen and growth factors. Overall proteolytic activity was also greatest at normoxia. Fibroblast growth factor stimulated urokinase production dose-dependently, but plasminogen activator inhibitor only minimally. Transforming growth factor-beta stimulated plasminogen activator inhibitor production dose-dependently but urokinase only at higher concentrations. These results suggest that both oxygen tension and growth factors may interact to modulate the proteolytic properties of the human retinal pigment epithelium.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume33
Issue number3
DOIs
StatePublished - Apr 26 2001

Keywords

  • Oxygen
  • Plasminogen activator
  • Plasminogen activator inhibitor-1
  • Retinal pigment epithelial cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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