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Amino Acids

, Volume 48, Issue 10, pp 2401–2410 | Cite as

Intracellular sources of ornithine for polyamine synthesis in endothelial cells

  • Hui Li
  • Cynthia J. Meininger
  • Fuller W. Bazer
  • Guoyao Wu
Original Article
Part of the following topical collections:
  1. Polyamines and TGases

Abstract

Polyamines are essential for proliferation of endothelial cells (EC) and angiogenesis. This study was conducted to identify the metabolic source(s) of ornithine for polyamine synthesis in EC, using Nω-hydroxy-nor-l-arginine (Nor-NOHA, an inhibitor of arginase) and gabaculine (an inhibitor of ornithine aminotransferase; OAT). Nor-NOHA inhibited arginase with an IC50 value of 10 µM for intact EC. Nor-NOHA (0.5 mM) alone inhibited arginase activity in EC by 98 %, increased total cellular concentrations of arginine by 14 %, and decreased total cellular concentrations of ornithine, putrescine and spermidine by 17, 65 and 74 %, respectively. Arginine and glutamine contributed to 73 and 26 % of the ornithine produced by EC, respectively. Gabaculine (1 mM) alone decreased the total cellular concentrations of arginine, ornithine, putrescine, and spermidine by 14, 96, 32, and 42 %, respectively. A combination of both Nor-NOHA and gabaculine completely blocked ornithine production in EC, resulting in no detectable cellular ornithine and almost complete depletion of cellular putrescine and spermidine. Addition of 0.5 mM ornithine restored the intracellular concentrations of polyamines in EC treated with Nor-NOHA plus gabaculine, indicating that Nor-NOHA and gabaculine did not inhibit ornithine decarboxylase activity. Our results suggest that the arginase and OAT pathways are the exclusive sources of ornithine in EC when there is little extracellular ornithine and that there is intracellular compartmentalization of arginine and ornithine for endothelial synthesis of polyamines.  These novel findings may have important implications for improving placental vascular growth, wound healing, and cancer therapy.

Keywords

Arginase Ornithine Polyamines Endothelial cells 

Abbreviations

EC

Endothelial cells

Nor-NOHA

Nω-hydroxy-nor-l-arginine

ODC

Ornithine decarboxylase

OAT

Ornithine aminotransferase

P5C

Pyrroline-5-carboxylate

Notes

Acknowledgments

This research was supported, in part, by Agriculture and Food Research Initiative Competitive Grants of (2015-67015-23276) of the USDA National Institute of Food and Agriculture, American Heart Association (10GRNT4480020 and 11GRNT7930004), and Texas A&M AgriLife Research (H-82000).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

This study involved the cultures of an existing cell line and did not require an Animal Use Protocol.

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Hui Li
    • 1
  • Cynthia J. Meininger
    • 2
  • Fuller W. Bazer
    • 1
  • Guoyao Wu
    • 1
    • 2
  1. 1.Department of Animal ScienceTexas A&M UniversityCollege StationUSA
  2. 2.Department of Medical PhysiologyTexas A&M UniversityCollege StationUSA

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