A procyanidin trimer, C1, promotes NO production in rat aortic endothelial cells via both hyperpolarization and PI3K/Akt pathways.
Procyanidins, which are condensed catechins, have been elucidated as absorbable polyphenols, but their health-benefits remain unclear. The aim of this study was, thus, to clarify the efficacy and mechanism of each procyanidin oligomer in NO activation in rat aortic endothelial cells (RAECs). Treatment of RAECs with 50μM procyanidin C1 (4β→8 trimer) resulted in a time- and dose-dependent hyperpolarization using the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, while no effect was observed for (-)-epicatechin (a monomer) and procyanidin B2 (4β→8 dimer). The C1-induced hyperpolarization was inhibited by iberiotoxin, a specific inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, as well as 2-aminoethyl diphenylborinate (2-APB), a store-operated Ca(2+) entry inhibitor. Procyanidin C1 caused a significant increase in NO production from RAECs via phosphorylation of both eNOS and Akt, and the effect was completely inhibited by N(G)-monomethyl-l-arginine or combined treatment with iberiotoxin and the phosphatidylinositol 3-kinase (PI3K) specific inhibitor, wortmannin, as well as combined treatment with 2-APB and wortmannin. Taken together, these findings provide critical evidence that procyanidin C1, but not B2, has potential to induce NO production in RAECs via both Ca(2+)-dependent BK(Ca) channel-mediated hyperpolarization and Ca(2+)-independent PI3K/Akt pathways.
Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan.
Eui-Baek
EB
Byun
Teruaki
T
Ishikawa
Aki
A
Suyama
Masaya
M
Kono
Shohei
S
Nakashima
Tomomasa
T
Kanda
Takahisa
T
Miyamoto
Toshiro
T
Matsui
D000818:Animals; D001011:Aorta / Q000166:cytology*; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D058105:Polymerization; D026902:Potassium Channel Blockers / Q000494:pharmacology; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D044946:Biflavonoids; D026902:Potassium Channel Blockers; D044945:Proanthocyanidins; D009569:Nitric Oxide; C017674:procyanidin; D002392:Catechin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium