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

Activities of arginase I and II are limiting for endothelial cell proliferation 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-α-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 μM 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. ornithine polyamines cell transfection Footnotes This work was supported in part by American Heart Associations Grants 95013030, 9740124N, and 98G-022 (to G. Wu and C. J. Meininger), Juvenile Diabetes Foundation International Grant 1-2000-437 (to C. J. Meininger and G. Wu), and National Institute of General Medical Science Grant R01 GM-57384 (to S. M. Morris, Jr.). G. Wu is an Established Investigator of the American Heart Association. Address for reprint requests and other correspondence: G. Wu, Dept. of Animal Science, Texas A&M Univ., 2471 TAMU, College Station, TX 77843-2471 (E-mail: g-wu@tamu.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Regulatory, Integrative and Comparative Physiology The American Physiological Society

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

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6119
eISSN
1522-1490
Publisher site
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Abstract

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-α-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 μM 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. ornithine polyamines cell transfection Footnotes This work was supported in part by American Heart Associations Grants 95013030, 9740124N, and 98G-022 (to G. Wu and C. J. Meininger), Juvenile Diabetes Foundation International Grant 1-2000-437 (to C. J. Meininger and G. Wu), and National Institute of General Medical Science Grant R01 GM-57384 (to S. M. Morris, Jr.). G. Wu is an Established Investigator of the American Heart Association. Address for reprint requests and other correspondence: G. Wu, Dept. of Animal Science, Texas A&M Univ., 2471 TAMU, College Station, TX 77843-2471 (E-mail: g-wu@tamu.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2002 the American Physiological Society

Journal

AJP - Regulatory, Integrative and Comparative PhysiologyThe American Physiological Society

Published: Jan 1, 2002

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