Activities of arginase I and II are limiting for endothelial cell proliferation.
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.
Li
Hui
H
Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, Texas 77843-2471, USA.
Meininger
Cynthia J
CJ
Kelly
Katherine A
KA
Hawker
James R
JR
Morris
Sidney M
SM
Wu
Guoyao
G
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D000518:Eflornithine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007763:Lac Operon; D009952:Ornithine / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D014162:Transfection
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009952:Ornithine; D001119:Arginase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine