TY - JOUR
T1 - Effects of (-)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins
AU - Moreno-Ulloa, Aldo
AU - Cid, Armando
AU - Rubio-Gayosso, Ivan
AU - Ceballos, Guillermo
AU - Villarreal, Francisco
AU - Ramirez-Sanchez, Israel
N1 - Funding Information:
We would like to acknowledge the editorial help provided by Dr. Laurence Brunton. Study was supported by NIH R24 DK092154, R01 HL43617 and P60 MD00220 provided to Dr. F. Villarreal, CONACyT research grant # 129889 and an unrestricted gift to Dr. Ceballos by Cardero Therapeutics Inc.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Impaired mitochondrial function represents an early manifestation of endothelial dysfunction and likely contributes to the development of cardiovascular diseases (CVD). The stimulation of mitochondrial function and/or biogenesis is seen as a means to improve the bioenergetic and metabolic status of cells and thus, reduce CVD. In this study we examined the capacity of the flavanol (-)-epicatechin and two novel derivatives to enhance mitochondrial function and protein levels in cultured bovine coronary artery endothelial cells. As nitric oxide production by endothelial cells is suspected in mediating mitochondria effects (including biogenesis), we also examined the dependence of responses on this molecule using an inhibitor of nitric oxide synthase. Results indicate that the flavanol (-)-epicatechin and derivatives are capable of stimulating mitochondrial function as assessed by citrate synthase activity as well as induction of structural (porin, mitofilin) and oxidative phosporylation protein levels (complex I and II). Effects were blocked by the use of the chemical inhibitor of the synthase thus, evidencing a role for nitric oxide in mediating these effects. The results observed indicate that the three agents are effective in enhancing mitochondria function and protein content. The effects noted for (-)-epicatechin may serve to explain the healthy effects on cardiometabolic risk ascribed to the consumption of cocoa products.
AB - Impaired mitochondrial function represents an early manifestation of endothelial dysfunction and likely contributes to the development of cardiovascular diseases (CVD). The stimulation of mitochondrial function and/or biogenesis is seen as a means to improve the bioenergetic and metabolic status of cells and thus, reduce CVD. In this study we examined the capacity of the flavanol (-)-epicatechin and two novel derivatives to enhance mitochondrial function and protein levels in cultured bovine coronary artery endothelial cells. As nitric oxide production by endothelial cells is suspected in mediating mitochondria effects (including biogenesis), we also examined the dependence of responses on this molecule using an inhibitor of nitric oxide synthase. Results indicate that the flavanol (-)-epicatechin and derivatives are capable of stimulating mitochondrial function as assessed by citrate synthase activity as well as induction of structural (porin, mitofilin) and oxidative phosporylation protein levels (complex I and II). Effects were blocked by the use of the chemical inhibitor of the synthase thus, evidencing a role for nitric oxide in mediating these effects. The results observed indicate that the three agents are effective in enhancing mitochondria function and protein content. The effects noted for (-)-epicatechin may serve to explain the healthy effects on cardiometabolic risk ascribed to the consumption of cocoa products.
KW - Endothelial cells
KW - Epicatechin
KW - Mitochondria
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=84879689589&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2013.05.079
DO - 10.1016/j.bmcl.2013.05.079
M3 - Artículo
C2 - 23791569
SN - 0960-894X
VL - 23
SP - 4441
EP - 4446
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 15
ER -