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謝辞
本論文を校閲、添削され、御懇切なる御指導を頂きました九州大学大学院農
学研究院生命機能科学部門発酵化学教授 竹川薫先生に深甚なる感謝の意を表
します。また、本論文を校閲・添削され、御指導をいただいた九州大学大学院
農学研究院生命機能科学部門細胞制御工学教授 片倉喜範先生、九州大学大学
院農学研究院生命機能科学部門発酵化学准教授 樋口裕次郎先生に深く感謝申
し上げます。
本研究の多くは細胞実験によって行われました。細胞実験の手技、手法を御
教授下さいました大分大学医学部マトリックス医学研究室 松尾哲孝准教授に
厚く御礼申し上げます。
本研究は全て三和酒類株式会社研究所において行われたものであり、会社か
らの支援なくして実施することはできませんでした。このような機会を与えて
下さった三和酒類株式会社の役員様をはじめ、従業員の皆様に深く感謝の意を
表します。特に、学位取得の希望を申し上げた際、竹川教授を快く御紹介下さ
り、また多大なる御支援を下さった髙下秀春取締役に厚く御礼申し上げま
す。
さらに入社から今日まであらゆる場面で多大なる御指導と御鞭撻を賜り、本
論文をまとめるに際しても御支援を頂きました三和酒類株式会社三和研究所
外薗英樹副所長に深く感謝の意を表します。
最後に入社以来、あらゆる場面で実験に関する御助言を下さった三和酒類株
式会社三和研究所ウェルビーイング研究室 中村彰宏室長、クロスオーバーセ
ンター 丸岡生行主任研究員に深く御礼を申し上げます。
156
要約（英文）
We investigated the effective use of fermented barley extract (FBE), which is the liquid that
remains after removing solids from barley shochu lees. A sample of FBE purified by a synthetic
adsorbent was fractionated using high-performance liquid chromatography. Human chondrosarcoma
cells were exposed to the FBE fractions and the expression of cartilage degrading enzyme matrix
metalloproteinase (MMP)-13 mRNA was quantified by real-time polymerase chain reaction (PCR).
pEPYP, a pyroglutamyl tetrapeptide in fraction FBE-P40-5, significantly suppressed the mRNA and
protein expression of cartilage degrading enzyme MMP-13. Furthermore, pEPYP significantly
enhanced interleukin 10 mRNA and protein expression in lymphoblastic leukemia T cells. When
pEPYP was orally administered to rheumatoid arthritis model rats, the results indicated that the
edema score and anti-type II collagen antibody IgG level decreased. Ingestion of pEPYP by humans
with knee joint discomfort significantly reduced knee pain and stiffness. This result suggests that
pEPYP intake suppresses arthritis. Similarly, exposure of human colorectal adenocarcinoma (Caco2) cells to the pyroglutamylproline (pEP) contained in FBE-P60-4-6 significantly promoted
expression of ATP binding cassette subfamily G member (ABCG)2 mRNA and protein.
Immunostaining provided visual confirmation that ABCG2 was expressed in the plasma membrane
of Caco-2 cells. This result suggests that pEP intake could lower serum uric acid levels.
FBE is an excellent medium for culturing lactic acid bacteria, and γ-aminobutyric acid (GABA)
is produced via a fermentation process using FBE as a medium. Using normal human dermal
fibroblasts, we confirmed the effect of GABA on the expression of genes involved in skin elasticity
by real-time PCR. GABA significantly promoted COL1A1 mRNA expression and significantly
decreased MMP-1 mRNA expression. Significant increases in ELN and FBN-1, FBN-2, and FBLN5 mRNA were also observed. Increased expression of elastin protein was visually confirmed by
immunofluorescent staining. These results suggest that GABA intake directly maintains skin
elasticity. Proliferation of mouse myoblasts exposed to GABA was significantly increased. GABA
also significantly increased MyoD and PGC-1α mRNA and protein expression and significantly
decreased myostatin mRNA and protein expression. These results suggest that GABA may not only
directly promote an increase in, but also prevent the loss of skeletal muscle mass.
157
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