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Related Experiment Videos

Angiogenin activates endothelial cell phospholipase C.

R Bicknell1, B L Vallee

  • 1Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|August 1, 1988
PubMed
Summary

Low concentrations of the protein angiogenin activate phospholipase C in endothelial cells, initiating signaling pathways crucial for blood vessel formation (angiogenesis). Higher concentrations, however, show reduced cellular response, suggesting a regulatory mechanism.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Medicine

Background:

  • Angiogenin is a protein involved in blood vessel formation.
  • Endothelial cells play a critical role in angiogenesis.
  • Signaling pathways within endothelial cells regulate vascularization.

Purpose of the Study:

  • To investigate the effect of angiogenin on endothelial cell signaling.
  • To determine the dose-dependent response of endothelial cells to angiogenin.
  • To explore the relationship between angiogenin's enzymatic activity and its angiogenic function.

Main Methods:

  • Cultured endothelial cells (pulmonary artery, umbilical vein, capillary) were treated with varying concentrations of angiogenin.
  • Intracellular levels of 1,2-diacylglycerol and inositol trisphosphate were measured.

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  • Chemical modification of angiogenin's active site and inhibition with placental ribonuclease inhibitor were employed.
  • Angiogenic activity was assessed using classical angiogenesis assays.

    • Main Results:

    • Low concentrations of angiogenin activated inositol-specific phospholipase C in endothelial cells, increasing intracellular 1,2-diacylglycerol and inositol trisphosphate.
    • The response was dose-dependent, with optimal activation at ng/ml concentrations and a decrease at higher levels.
    • Inhibition of angiogenin's ribonucleolytic activity abolished phospholipase C activation and angiogenic potential.
    • In vivo, endothelial cells encounter higher angiogenin concentrations than optimal for cellular response, indicating potential rate-limiting factors.

    Conclusions:

    • Angiogenin activates endothelial cell phospholipase C at low concentrations, contributing to angiogenesis.
    • Angiogenin's ribonucleolytic activity is essential for its signaling and angiogenic functions.
    • A potential rate-limiting step, possibly a surface receptor, regulates the cellular response to high angiogenin concentrations in vivo.