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(−)‐Epicatechin induces calcium and translocation independent eNOS activation in endothelial cells via AKT/HSP90
Author(s) -
Ramirez-Sanchez Israel,
Ceballos Guillermo,
Villarreal Francisco
Publication year - 2012
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.26.1_supplement.1056.16
Subject(s) - enos , protein kinase b , phosphorylation , chemistry , chromosomal translocation , microbiology and biotechnology , nitric oxide , calcium , pi3k/akt/mtor pathway , medicine , endothelial nos , endocrinology , signal transduction , biochemistry , nitric oxide synthase , biology , gene
The consumption of cacao‐derived products provides beneficial cardiovascular effects. Vascular actions of cocoa are related to enhanced nitric oxide (NO) production. These actions can be reproduced by the administration of the flavanol (−)‐epicatechin (EPI). EPI is capable of inducing the synthesis of NO via endothelial NO synthase (eNOS) activation in human coronary artery endothelial cells (HCAEC) through PI3K/AKT/PKA and Ca 2+ ‐CaM/CaMKII pathways. To further understand the mechanisms behind the vascular action of EPI, we investigated the effects of Ca 2+ depletion on eNOS translocation, as well as on its activation/phosphorylation. Results demonstrate that under Ca 2+ ‐free conditions, EPI (but not BK) is capable of inducing NO production through eNOS phosphorylation. EPI‐induced translocation of eNOS from the plasmalemma was abolished upon Ca 2+ depletion. Thus, under these conditions, EPI can stimulate NO synthesis independent of calmodulin binding to eNOS and of its translocation into the cytoplasm. EPI is able to induce AKT activation as well as the physical association of HSP90‐eNOS. We also examined the effects of EPI on the NO/cGMP/vasodilator‐stimulated phosphoprotein (VASP) pathway in isolated Ca 2+ ‐deprived canine mesenteric arteries. EPI induces the activation of the vasorelaxation‐related pathway and the effects were blocked by nitro‐L‐arginine methyl ester (L‐NAME). Results indicate that EPI can uniquely modulate endothelial responses independently of calcium.