| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Nobuyuki Juntendo University, School of Medicine, Research Associate, 医学部, 助手
IKEJIMA Kenichi Juntendo University, School of Medicine, Research Associate, 医学部, 助手 (20317382)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Glycine, a non-essential amino acid, has been demonstrated to be preventive against ischemia-reperfusion injury in the liver. Since ischemia-reperfusion injury in the liver involves early damage of sinusoidal linage, we hypothesized that glycine protects sinusoidal endothelium from cell-death. In this study, we investigated the effect of glycine on apoptosis of sinusoidal endothelial cells caused by deprivation of vascular endothelial growth factor (VEGF). Cell-death was induced in primary cultured rat sinusoidal endothelial cells by deprivation of VEGF, and apoptosis was detected by TUNEL staining. Glycine prevented increases in TUNEL-positive cells following VEGF deprivation. Further, strychnine, a putative glycine receptor antagonist, inhibited the effect of glycine. Moreover, VEGF deprivation decreased Bcl-2 protein levels, whereas glycine maintained Bcl-2 protein levels in the absence of VEGF. These findings indicated that antiapoptotic effect of glycine on endothelial cells involves glycine receptor and Bcl-2, Next, we evaluated whether glycine prevents inflammation in the gut using an experimental colitis model induced by 2, 4, 6-trinitrobenzene sulphonic acid (TNBS) in the rat. A diet containing glycine (5%) ameliorated body weight loss and diarrhea induced by an intracolonic injection of TNBS. Dietary glycine improved both macroscopic and histopathological scores, as well as tissue myeloperoxidase activity, following TNBS treatment significantly. Further, glycine blunted the induction of inflammatory cytokines (IL- 1β and TNF-α) and chemokines (CINC and MIP-2) dramatically. These findings suggest a possibility that glycine is useful for the treatment of inflammatory bowel diseases as an immuno-modulating nutrient.
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