2001 Fiscal Year Final Research Report Summary
Exploitation of anti-alopecic and hair-growth promoting peptides
| Project/Area Number |
12559005
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
広領域
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOSHIKAWA Masaaki Kyoto University, Graduate School of Agriculture, Professor, 農学研究科, 教授 (50026572)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHATA Kyouya Okayama University, Faculty of Agriculture, Professor, 農学部, 教授 (30243497)
TUJI Akira Kanazawa University, Faculty of Pharmacy, Professor, 薬学部, 教授 (10019664)
TAKENAKA Yasuyuki Kyoto University, Graduate School of Agriculture, Instructor, 農学研究科, 助手 (20273518)
TAKAHASHI Tomoya Kyowa Hakko Kogyo Co., Ltd., Tsukuba Institute, Chief Researcher, 筑波研究所, 主任研究員
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| Project Period (FY) |
2000 – 2001
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| Keywords | alopecia / fMLP / immunostimulating peptide / soybean / cancer chemotherapy / histamine / IL-1 / NF-κB |
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| Research Abstract |
Anti-alopecia or hair growth issue is important to enjoy comfortable life. Especially, alopecia induced by cancer-chemotherapy is a serious problem since it impairs quality of life of patients. Exploitation of anti-alopecia agents has been demanded under these circumstances. We found that soymetide-4, an immunostimulating peptide derived from soybean (β-conglycinin, prevented alopecia induced by etoposide, an anti-cancer agent, after oral administration in sucling rats.
We also found that anti-alopecic activity of soymetide-4 was mediated by receptors for fMLP, a chemotactic peptide derived from bacteria. Although fMLP was ineffective after oral administra-tion, it prevented the alopecia after intravenous administration. There are two subtypes, FPR (high affinity site) and FPRL1 (low affinity site) in human fMLP receptor. An FPRLl-selective peptide MMK-1 also prevented alopecia induced by etoposide suggesting the importance of the low affinity site.
The anti-alopecia effect of fMLP was prevented by pyrilarnine, an antagonist for histamine H1 receotor, and Lys-D-Pro-Thr, a inhibitor for IL-1 suggesting the involvement of histamine and IL-1. The anti-alopecia effect was also prevented by pyrrolidine dithiocarbamate ammonium suggesting that the activation of NF-κB was important for the anti-alopecia effect by fMLP. Apoptosis of hair follicle cells induced by etoposide, an inhibitor for topoisomerase II, might be prevented as a consequence of NF-κB activation leading to the anti-alopecia effect.
We also designed tri- and dipeptide analogues of soymetide-4, which might be more suited for oral administration. These analogues could be found in enzymatic digests of food proteins or introduced into food proteins by genetic engineering.
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