Activities of arginase I and II are limiting for endothelial cell proliferation

Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R64-9. doi: 10.1152/ajpregu.2002.282.1.R64.

Abstract

Polyamines are essential for cell proliferation; therefore, we hypothesized that arginase I or arginase II activities, via production of ornithine for polyamine synthesis, may be limiting for proliferation of endothelial cells (EC). Bovine coronary venular EC stably transfected with a lacZ gene (lacZ-EC, control), rat arginase I cDNA (AI-EC), or mouse arginase II cDNA (AII-EC) were utilized to test this hypothesis. Cell-proliferation assays showed that EC proliferation was markedly increased in AI-EC and AII-EC compared with lacZ-EC. Expression of proliferating cell nuclear antigen was also enhanced in AI-EC and AII-EC. DL-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, was used to establish that increased polyamine synthesis was involved in mediating the enhanced growth of AI-EC and AII-EC. Addition of 5 mM DFMO to the culture medium completely abolished the differences in cellular putrescine concentrations and reduced the differences in spermidine concentrations among AI-EC, AII-EC, and lacZ-EC. The DFMO treatment also prevented an increase in AI-EC and AII-EC proliferation compared with lacZ-EC. Addition of 10 and 50 microM putrescine dose-dependently increased AI-EC, AII-EC, and lacZ-EC growth to the same extent. These results demonstrate that either arginase isoform can potentially play a role in modulating EC proliferation by regulating polyamine synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / metabolism*
  • Cattle
  • Cell Division / physiology
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Eflornithine / pharmacology
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / enzymology*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lac Operon
  • Ornithine / metabolism
  • Ornithine Decarboxylase Inhibitors
  • Polyamines / metabolism
  • Putrescine / metabolism
  • Spermidine / metabolism
  • Transfection

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • Ornithine
  • Arginase
  • Spermidine
  • Putrescine
  • Eflornithine