Staurosporine promotes endothelial cell assembly and fak phosphorylation during in vitro angiogenesis

Sima T. Tarzami, Susie Shao Hsu Hsieh, Michail A. Esterman, Pal Singh Jai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In the present study, we report that staurosporine, a known PKC inhibitor, enhanced in vitro angiogenesis. Endothelial cells plated in a three-dimensional matrix formed cords and enclosed structures within 4-6 hours. The cells in cord structures became elongated during the subsequent incubation. Tube formation was confirmed by confocal microscopy. Addition of VEGF enhanced the early responses of endothelial cells, leading to enhanced formation of cords. Staurosporine unexpectedly also enhanced the early endothelial responses, leading to faster alignment of cells and assembly into tube-like structures. At concentrations inhibitory to endothelial cell PKC activity, staurosporine produced 91% and 203% increases in the number of cords and the enclosed structures, respectively, as compared to the controls. Other selective inhibitors of PKC did not stimulate in vitro angiogenesis in the absence or presence of VEGF. Further investigation showed that inhibition of PI-3 kinase and Raf-1 significantly reduced the effects of staurosporine. Staurosporine-induced in vitro angiogenesis required integrins α2 and αvβ3 and was associated with significantly enhanced FAK phosphorylation. These data indicate that staurosporine enhances in vitro angiogenesis by a means unrelated to its PKC inhibition. The data suggest that enhancement of in vitro angiogenesis by staurosporine involves integrin-mediated signaling, including the stimulation of FAK phosphorylation.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume45
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Staurosporine
Endothelial Cells
Phosphorylation
Integrins
Vascular Endothelial Growth Factor A
Proto-Oncogene Proteins c-raf
In Vitro Techniques
Phosphatidylinositol 3-Kinases
Confocal Microscopy

Keywords

  • Angiogenesis
  • FAK phosphorylation
  • Staurosporine

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Staurosporine promotes endothelial cell assembly and fak phosphorylation during in vitro angiogenesis. / Tarzami, Sima T.; Hsieh, Susie Shao Hsu; Esterman, Michail A.; Jai, Pal Singh.

In: Journal of Cardiovascular Pharmacology, Vol. 45, No. 1, 01.2005, p. 22-29.

Research output: Contribution to journalArticle

Tarzami, Sima T. ; Hsieh, Susie Shao Hsu ; Esterman, Michail A. ; Jai, Pal Singh. / Staurosporine promotes endothelial cell assembly and fak phosphorylation during in vitro angiogenesis. In: Journal of Cardiovascular Pharmacology. 2005 ; Vol. 45, No. 1. pp. 22-29.
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