Pharmacological inhibition of poly(ADP-ribose) polymerase activity down-regulates the expression of syndecan-4 and Id-1 in endothelial cells

Pedro M. Lacal, Lucio Tentori, Alessia Muzi, Federica Ruffini, Annalisa Susanna Dorio, Weizheng Xu, Diego Arcelli, Jie Zhang, Grazia Graziani

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Poly(ADP-ribose) polymerase (PARP) is a family of nuclear proteins which regulate a number of cell functions, such as DNA repair, transcription, remodelling of chromatin structure, cell division and cell death. We and others have recently demonstrated that down-regulation of cellular PARP activity, using pharmacological inhibitors, impairs a number of endothelial functions and angiogenesis. In the present study, we investigated the potential mechanisms underlying the anti-angiogenic effect exerted by the potent PARP inhibitor GPI 15427, analyzing gene expression in human endothelial cells shortly after treatment with this compound. Analysis of gene and protein expression indicated that a 2-h exposure of human endothelial cells to GPI 15427 induced a rapid decrease of syndecan-4 (SDC-4), a transmembrane protein involved in modulation of cell signalling during angiogenesis that plays a role in endothelial cell migration and adhesion. Moreover, treatment with the PARP inhibitor induced a reduction of a helix-loop-helix transcription factor, the inhibitor of DNA binding-1 (Id-1), also implicated in the control of endothelial functions. We suggest that the inhibitory effect exerted by GPI 15427 on the angiogenic process is likely due to the reduced activity of specific transcription factors, such as Oct-1 and CREB that contribute to the regulation of SDC-4 and Id-1 expression, respectively. In conclusion, these results strongly suggest that PARP activity is capable of modulating molecules required for endothelial cell migration, adhesion, proliferation or differentiation during the angiogenic process.

Original languageEnglish
Pages (from-to)861-872
Number of pages12
JournalInternational Journal of Oncology
Volume34
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Syndecan-4
Poly(ADP-ribose) Polymerases
Down-Regulation
Endothelial Cells
Pharmacology
Cell Adhesion
Cell Movement
Transcription Factors
Gene Expression
Chromatin Assembly and Disassembly
Nuclear Proteins
DNA Repair
Cell Division
Proteins
Cell Death
Cell Count
DNA
GPI 15427

Keywords

  • Angiogenesis
  • Endothelial cell
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pharmacological inhibition of poly(ADP-ribose) polymerase activity down-regulates the expression of syndecan-4 and Id-1 in endothelial cells. / Lacal, Pedro M.; Tentori, Lucio; Muzi, Alessia; Ruffini, Federica; Dorio, Annalisa Susanna; Xu, Weizheng; Arcelli, Diego; Zhang, Jie; Graziani, Grazia.

In: International Journal of Oncology, Vol. 34, No. 3, 2009, p. 861-872.

Research output: Contribution to journalArticle

Lacal, Pedro M. ; Tentori, Lucio ; Muzi, Alessia ; Ruffini, Federica ; Dorio, Annalisa Susanna ; Xu, Weizheng ; Arcelli, Diego ; Zhang, Jie ; Graziani, Grazia. / Pharmacological inhibition of poly(ADP-ribose) polymerase activity down-regulates the expression of syndecan-4 and Id-1 in endothelial cells. In: International Journal of Oncology. 2009 ; Vol. 34, No. 3. pp. 861-872.
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