title: The bioavailable octapeptide Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro stimulates nitric oxide synthesis in vascular endothelial cells.
abstract: 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.
authors.affiliation: R&D Center, Nippon Meat Packers Inc, Tsukuba, Ibaraki 300-2646, Japan. kazu.shimizu@nipponham.co.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimizu
authors.forename: Mikako
authors.initials: M
authors.lastname: Sato
authors.forename: Youzuo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kouguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahata
authors.forename: Fumiki
authors.initials: F
authors.lastname: Morimatsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: 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
chemical_list: D009842:Oligopeptides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III