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.

Summary Effects of chicken collagen hydrolysate (CCH) on atherogenesis in apolipoprotein E-deficient C57BL/6.KOR-ApoE shl mice were investigated in this paper. The mice were fed on either a normal CE-2 diet (control group) or a diet containing 10% CCH (CCH group) for 12 wk. Compared with that of the control, the amount of total plasma cholesterol, total hepatic cholesterol and hepatic triglycerides in the CCH group was reduced by 14.4, 24.7 and 42.8%, respectively. Histological analysis results showed that the abundance of diffuse hepatic lipid droplets and fat vacuoles was decreased in the CCH group. Meanwhile, the concentration of proinflammatory cytokines in the CCH group plasma, including interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), and tumor necrosis factor-␣ (TNF-␣ ), was downregulated by 43.4, 17.9 and 24.1%, respectively. The present results suggested that CCH treatment might help prevent atherosclerosis through not only its lipid-lowering effects but also inhibiting expression of inflammatory cytokines.

We investigated the effects of a chicken collagen hydrolysate (CCH) on the circulation system in humans. A total of 58 subjects with either mild hypertension (systolic blood pressure (SBP) of 140-159 mmHg or diastolic blood pressure (DBP) 90-99 mmHg) or high-normal blood pressure (SBP 130-139 mmHg or DBP 85-89 mmHg) were assigned to two groups, one involving a placebo and the other, the test food (including CCH of 2.9 g/d). The parameters related to each subject's circulation system were monitored over the study period of 18 weeks. The Δbrachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness and marker of vascular damage, was significantly lower in the test food group than in the placebo group during the treatment period. The blood pressure in the test food group was also significantly lower than that in the placebo group, while the serum nitrogen oxide was higher in the test food group after the treatment. These results suggest that CCH exerted modulatory effects on the human circulation system.

In mice, glial cell line-derived neurotrophic factor (GDNF) is essential for normal spermatogenesis and in vitro culture of spermatogonial stem cells. In murine testes, GDNF acts as paracrine factor; Sertoli cells secrete it to a subset of spermatogonial cells expressing its receptor, GDNF family receptor α1 (GFRα1). However, in fish, it is unclear what types of cells express gdnf and gfrα1. In this study, we isolated the rainbow trout orthologues of these genes and analyzed their expression patterns during spermatogenesis. In rainbow trout testes, gdnf and gfrα1 were expressed in almost all type A spermatogonia (ASG). Noticeably, unlike in mice, the expression of gdnf was not observed in Sertoli cells in rainbow trout. During spermatogenesis, the expression levels of these genes changed synchronously; gdnf and gfrα1 showed high expression in ASG and decreased dramatically in subsequent developmental stages. These results suggested that GDNF most likely acts as an autocrine factor in rainbow trout testes.