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2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran promotes endothelial nitric oxide synthase activity in human endothelial cells
- Source :
-
Biochemical Pharmacology . Sep2012, Vol. 84 Issue 6, p804-812. 9p. - Publication Year :
- 2012
-
Abstract
- Abstract: Endothelial nitric oxide synthase (eNOS) mediates important vaso-protective and immunomodulatory effects. Aim of this study was to examine whether lignan derivatives isolated from the roots of the anti-inflammatory medicinal plant Krameria lappacea influence eNOS activity and endothelial nitric oxide (NO) release. The study was performed using cultured human umbilical vein endothelial cells (HUVECs) and HUVEC-derived EA.hy926 cells. Among the eleven isolated compounds only 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran (DPPB) was able to increase eNOS enzyme activity. DPPB (1–10μM) treatment for 24h induced a significant and dose-dependent increase in eNOS activity as determined by the [14C]l-arginine/[14C]l-citrulline conversion assay. Immunoblotting studies further revealed a time-dependent DPPB-induced increase in eNOS-Ser1177 and decrease in eNOS-Thr495 phosphorylation, as well as increased AMPK phosphorylation at Thr172, whereas Akt phosphorylation at Ser473 was not affected. Si-RNA-mediated knockdown of AMPK and inhibition of CaMKKβ by STO 609, as well as intracellular Ca2+ chelation by Bapta AM abolished the stimulating effect of DPPB on eNOS-Ser1177 and AMPK-Thr172 phosphorylation. Furthermore, we could show that DPPB increases intracellular Ca2+ concentrations assessed with the fluorescent dye Fluo-3-AM. DPPB enhances eNOS activity and endothelial NO release by raising intracellular Ca2+ levels and increases signaling through a CaMKKβ–AMPK dependent pathway. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 84
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 78430599
- Full Text :
- https://doi.org/10.1016/j.bcp.2012.06.029