Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a key role in angiogenesis. Barley-derived (1.3) β-D-glucan (β-D-glucan) is a natural water-soluble polysaccharide with antioxidant properties. To explore the effects of β-D-glucan on MnSOD-related angiogenesis under oxidative stress, we tested epigenetic mechanisms underlying modulation of MnSOD level in human umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo. Long-term treatment of HUVECs with 3% w/v β-D-glucan significantly increased the level of MnSOD by 200±2% compared to control and by 50±4% compared to untreated H2O2-stressed cells. β-D-glucan-treated HUVECs displayed greater angiogenic ability. In vivo, 24h-treatment with 3% w/v β-D-glucan rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide anion (O2-) and an increased survival under oxidative stress. In addition, β-D-glucan prevented the rise of hypoxia inducible factor (HIF)1-α under oxidative stress. The level of histone H4 acetylation was significantly increased by β-D-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor of class I histone deacetylases (HDACs I), did not activate MnSOD-related angiogenesis and did not impair β-D-glucan effects. In conclusion, 3% w/v β-D-glucan activates endothelial expression of MnSOD independent of histone acetylation level, thereby leading to adequate removal of O2-, cell survival and angiogenic response to oxidative stress. The identification of dietary β-D-glucan as activator of MnSOD-related angiogenesis might lead to the development of nutritional approaches for the prevention of ischemic remodeling and heart failure.
|Titolo:||Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment|
|Data di pubblicazione:||2015|
|Appare nelle tipologie:||1.1 Articolo su Rivista/Article|