The bioavailable octapeptide Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro stimulates nitric oxide synthesis in vascular endothelial cells.
Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro (GAXGLXGP, X: Hyp), an octapeptide contained in chicken collagen hydrolysate, inhibits angiotensin I-converting enzyme activity in vitro. Intestinal Caco-2 and bovine aortic endothelial cells (BAECs) were used to investigate whether the transported GAXGLXGP improves vascular function. When GAXGLXGP was added to the apical side of Caco-2 monolayers, the intact form of GAXGLXGP was released to the basolateral side without incorporation into the cells. This transport was energy-independent but was associated with tight junction permeability. GAXGLXGP was then added to BAECs, and endothelial nitric oxide (NO) synthase (eNOS) activation was examined. GAXGLXGP at a concentration of 10 microM stimulated production of NO during a 1 h incubation. This event involved phosphorylation of eNOS at Ser(1179) without a change in the total eNOS protein level. These findings indicate that GAXGLXGP absorbed intact through the intestinal epithelium has direct effects on eNOS activity in vascular endothelial cells, leading to NO synthesis, thereby suggesting the potential for improvement in vascular function.
Shimizu
Kazuo
K
R&D Center, Nippon Meat Packers Inc, Tsukuba, Ibaraki 300-2646, Japan. kazu.shimizu@nipponham.co.jp
Sato
Mikako
M
Zhang
Youzuo
Y
Kouguchi
Tomomi
T
Takahata
Yoshihisa
Y
Morimatsu
Fumiki
F
Shimizu
Makoto
M
D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009842:Oligopeptides / Q000493:pharmacokinetics
D009842:Oligopeptides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III