Dual actions of nitric oxide on angiogenesis: possible roles of PKC, ERK, and AP-1 |
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Authors: | Jones Michael K Tsugawa Kouji Tarnawski Andrzej S Baatar Dolgor |
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Institution: | Department of Medicine, Veterans Affairs Medical Center, 5901 East Seventh Street, Long Beach, CA 90822, USA. michael.jones4@med.va.gov |
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Abstract: | Regulation of angiogenesis by nitric oxide (NO) is controversial since NO has been shown to have both pro- and anti-angiogenic effects. In this study, we examined the effect of the NO donor, S-nitro-N-acetyl-penicillamine (SNAP), on in vitro angiogenesis, and the mechanisms involved: PKC activity, ERK and c-Jun phosphorylation, and AP-1 DNA binding activity, in microvascular endothelial cells. SNAP, at 0.5-4 mM, significantly and dose-dependently inhibited angiogenesis, PKC activity, and ERK and c-Jun phosphorylation up to 80%, 83%, and 63% and 73%, respectively. SNAP at concentrations > 2mM also abolished AP-1 binding activity. Lower concentrations of SNAP (0.1-0.3 mM) significantly increased angiogenesis, PKC activity, and ERK and c-Jun phosphorylation up to 46%, 60%, and 61% and 180%, respectively. These findings indicate that the dual pro- and anti-angiogenic actions of NO are dose-dependent and suggest that they are mediated by PKC and ERK acting on AP-1. |
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Keywords: | Angiogenesis Wound healing c-Jun Endothelial Gastric S-Nitro-N-acetyl-penicillamine SNAP |
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