TY - JOUR
T1 - (-)-Epicatechin-induced calcium independent eNOS activation
T2 - Roles of HSP90 and AKT
AU - Ramirez-Sanchez, Israel
AU - Aguilar, Hugo
AU - Ceballos, Guillermo
AU - Villarreal, Francisco
N1 - Funding Information:
Acknowledgments This study was supported by NIH AT4277, HL43617, P60-MD000220 grants to Dr. Villarreal.
PY - 2012/11
Y1 - 2012/11
N2 - Cardiovascular disease (CVD) is a leading determinant of mortality and morbidity in the world. Epidemiologic studies suggest that flavonoid intake plays a role in the prevention of CVD. Consumption of cocoa products rich in flavonoids lowers blood pressure and improves endothelial function in healthy subjects as well as in subjects with vascular dysfunction such as smokers and diabetics. The vascular actions of cocoa follow the stimulation of nitric oxide (NO). These actions can be reproduced by the administration of the cocoa flavanol (-)-epicatechin (EPI). Previously, using human endothelial cells cultured in calcium-free media, we documented EPI effects on eNOS independently of its translocation from the plasmalemma. To further define the mechanisms behind EPI-eNOS activation in Ca2+ -deprived endothelial cells, we evaluated the effects of EPI on the eNOS/AKT/HSP90 signaling pathway. Results document an EPI-induced phosphorylation/activation of eNOS, AKT, and HSP90. We also demonstrate that EPI induces a partial AKT/HSP90 migration from the cytoplasm to the caveolar membrane fraction. Immunoprecipitation assays of caveolar fractions demonstrate a physical association between HSP90, AKT, and eNOS. Thus, under Ca2+-free conditions, EPI stimulates NO synthesis via the formation of an active complex between eNOS, AKT, and HSP90.
AB - Cardiovascular disease (CVD) is a leading determinant of mortality and morbidity in the world. Epidemiologic studies suggest that flavonoid intake plays a role in the prevention of CVD. Consumption of cocoa products rich in flavonoids lowers blood pressure and improves endothelial function in healthy subjects as well as in subjects with vascular dysfunction such as smokers and diabetics. The vascular actions of cocoa follow the stimulation of nitric oxide (NO). These actions can be reproduced by the administration of the cocoa flavanol (-)-epicatechin (EPI). Previously, using human endothelial cells cultured in calcium-free media, we documented EPI effects on eNOS independently of its translocation from the plasmalemma. To further define the mechanisms behind EPI-eNOS activation in Ca2+ -deprived endothelial cells, we evaluated the effects of EPI on the eNOS/AKT/HSP90 signaling pathway. Results document an EPI-induced phosphorylation/activation of eNOS, AKT, and HSP90. We also demonstrate that EPI induces a partial AKT/HSP90 migration from the cytoplasm to the caveolar membrane fraction. Immunoprecipitation assays of caveolar fractions demonstrate a physical association between HSP90, AKT, and eNOS. Thus, under Ca2+-free conditions, EPI stimulates NO synthesis via the formation of an active complex between eNOS, AKT, and HSP90.
KW - Cocoa flavanols
KW - Endothelial cells
KW - Epicatechin
KW - eNOS
UR - http://www.scopus.com/inward/record.url?scp=84867333759&partnerID=8YFLogxK
U2 - 10.1007/s11010-012-1405-9
DO - 10.1007/s11010-012-1405-9
M3 - Artículo
C2 - 22865466
SN - 0300-8177
VL - 370
SP - 141
EP - 150
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -