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Inhibition of Poly (ADP‐ribose) Polymerase (PARP) by PJ‐34 regulates angiogenesis and VEGF‐induced MAPK‐signalling
Author(s) -
Olah Gabor,
Pyriochou Anastasia,
Papapetropoulos Andreas,
Szabo Csaba
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.746.10
Subject(s) - angiogenesis , mapk/erk pathway , poly adp ribose polymerase , protein kinase b , cancer research , kinase , phosphorylation , protein kinase a , p38 mitogen activated protein kinases , microbiology and biotechnology , biology , chemistry , polymerase , biochemistry , enzyme
Angiogenesis is a tightly regulated process known to be essential for normal embryonic development but also in physiological and pathological phenomena in the adult. Excessive and deregulated angiogenic response is thought to contribute to cancer, diabetic retinopathy, arthritis and psoriasis. The mitogen‐activated protein kinase (MAPK) pathway plays an essential role in the regulation of proliferation and survival. PARP is a multifunctional nuclear enzyme that also regulates transcription by affecting histones, DNA methylation and enhancer/promoter regions. Here we investigate the effects of poly (ADP‐ribose) polymerase (PARP) inhibition on angiogenesis and MAPK‐signalling. The results show that PARP inhibition with PJ34 reduces endothelial cell proliferation, migration and organization leading to decreased angiogenesis. PARP inhibition also decreased VEGF‐induced Akt, ERK1/2 and p38 phosphorylation. PARP‐1 inhibitors might be useful in disease states when suppression of angiogenesis and phosphorylation of MAPK‐pathway member is required.