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Bioorg Med Chem Lett. 2014 Jun 15;24(12):2749-52. doi: 10.1016/j.bmcl.2014.04.038. Epub 2014 Apr 19.

Cell membrane mediated (-)-epicatechin effects on upstream endothelial cell signaling: evidence for a surface receptor.

Author information

1
University of California, San Diego, Department of Medicine, San Diego, CA, United States; Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Miron, México, DF CP11340, Mexico.
2
Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, Tijuana, Baja California, Mexico.
3
University of California, San Diego, Department of Medicine, San Diego, CA, United States.
4
Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Miron, México, DF CP11340, Mexico.
5
University of California, San Diego, Department of Medicine, San Diego, CA, United States; Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Miron, México, DF CP11340, Mexico. Electronic address: israel.ramirez14@hotmail.com.

Abstract

The consumption of cacao-derived products, particularly in the form of dark chocolate is known to provide beneficial cardiovascular effects in normal individuals and in those with vascular dysfunction (reduced nitric oxide [NO] bioavailability and/or synthesis). Upstream mechanisms by which flavonoids exert these effects are poorly understood and may involve the participation of cell membrane receptors. We previously demonstrated that the flavanol (-)-epicatechin (EPI) stimulates NO production via Ca(+2)-independent eNOS activation/phosphorylation. We wished to investigate the plausible participation of a cell surface receptor using a novel cell-membrane impermeable EPI-Dextran conjugate (EPI-Dx). Under Ca(2+)-free conditions, human coronary artery endothelial cells (HCAEC) were treated for 10min with EPI or EPI-Dx at equimolar concentrations (100nM). Results demonstrate that both EPI and EPI-Dx induced the phosphorylation/activation of PI3K, PDK-1, AKT and eNOS. Interestingly, EPI-Dx effects were significantly higher in magnitude than those of EPI alone. The capacity of EPI-Dx to stimulate cell responses supports the existence of an EPI cell membrane receptor mediating eNOS activation.

KEYWORDS:

Endothelial cells; Epicatechin; PI3K/AKT; eNOS

PMID:
24794111
PMCID:
PMC4157920
DOI:
10.1016/j.bmcl.2014.04.038
[Indexed for MEDLINE]
Free PMC Article

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