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Grape seed extract enhances eNOS expression and NO production through regulating calcium‐mediated AKT phosphorylation in H 2 O 2 ‐treated endothelium
Author(s) -
Feng Zhe,
Wei RiBao,
Hong Quan,
Cui ShaoYuan,
Chen XiangMei
Publication year - 2010
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20100054
Subject(s) - enos , calcium , protein kinase b , extracellular , chemistry , nitric oxide , calcium in biology , microbiology and biotechnology , umbilical vein , reactive oxygen species , phosphorylation , intracellular , nitric oxide synthase , biochemistry , biology , organic chemistry , in vitro
GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H 2 O 2 (hydrogen peroxide)‐treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H 2 O 2 ‐treated cells in a dose‐dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose‐dependent manner in H 2 O 2 ‐treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 μM GSE, 2.0 μM TG (thapsigargin) and 20.0 μM 2‐APB (2‐aminoethoxydiphenyl borate) instead of 0.25 μM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p‐AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up‐regulation of eNOS and NO expression via inhibiting InsP 3 Rs (inositol 1,4,5‐trisphosphate receptors)‐mediated intracellular excessive calcium release and by activating p‐AKT in endothelial cells.