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Hair growth-stimulating and anti-alopecia mechanism of low molecular weight peptides

低分子肽的促生防脱发机制

基本信息

批准号：
18380081
负责人：
YOSHIKAWA Masaaki
金额：
$ 10.91万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Alopecia, hair loss induced by various types of causes, are serious problem in modern society since many people suffer from it. We have found that low molecular weight peptides derived from food proteins prevent alopecia induced by cancer chemotherapy and stimulate natural hair growth. Soymetide-4 (Met-Ile-Thr-Leu), an fMLP agonist peptide derived from soybean β-conglycinin and Gly-Leu-Phe, an immunostimulateing peptide derived from α-lactalbumin, are typical examples showing the preferable effect on hair as described above. We screened for new peptides among food proteins and investigated their mode of action in this study.Gly-Leu-Trp newly found in ovalbumin showed more potent anti-alopecia effect than Gly-Leu-Phe. Lactomedin 1(Phe-Lys-Asp-Cys-His-Leu-Ala-Arg), an immunostimulating peptide newly isolated from tryptic digest of human lactoferrin and acting through complementb C5a receptor, also showed anti-alopecia effect after ip. sdministration.We also found that Phe-Gly-Leu-Met-NH_2, a tetrapeptide at the carboxyl terminus of substance P, show anti-alopecia effect. This is very interesting since substance P itself is involved in aropecia areata induced by mental stress. It is also nteresting that this peptide has Met residue at the carboxyl terminus while soymetide and fMLP have it at their amino terminus.We found that angiotensin II (5-8), Ile-His-Pro-Phe, a tetrapeptide at the carboxyl terminus of angiotensin II, also show anti-alopecia effect..The anti-alopecia effect by these peptides were blocked by an antagonist for EP_4 receptor, ONO-AE_3-203. This suggests that the anti-alopecia effect is mediated by PGE_2 bound to EP_4 receptor..

脱发是由各种原因引起的脱发，是现代社会中的严重问题，因为许多人患有脱发。我们发现来自食物蛋白质的低分子量肽可以预防癌症化疗引起的脱发，并刺激头发自然生长。衍生自大豆β-伴大豆球蛋白的fMLP激动剂肽二甲双胍-4（Met-Ile-Thr-Leu）和衍生自α-乳白蛋白的免疫刺激肽Gly-Leu-Phe是显示如上所述对毛发的优选效果的典型实例。本研究从食物蛋白质中筛选新的多肽，并对其作用机制进行了研究，发现在卵清蛋白中新发现的Gly-Leu-Trp比Gly-Leu-Phe具有更强的抗脱发作用。乳介素1（Lactomedin 1，Phe-Lys-Asp-Cys-His-Leu-Ala-Arg）是从人乳铁蛋白的胰蛋白酶消化物中分离得到的一种免疫刺激肽，通过补体C5 a受体发挥作用。P物质羧基端的四肽Phe-Gly-Leu-Met-NH_2也有抗脱发作用。这是非常有趣的，因为P物质本身涉及由精神压力引起的aroparteriata。同时发现，血管紧张素Ⅱ（5-8）、Ile-His-Pro-Phe（血管紧张素Ⅱ羧基端的四肽）也具有抗脱发作用。EP_4受体拮抗剂ONO-AE_3-203可阻断这些肽的抗脱发作用。提示PGE_2的抗脱发作用是通过与EP_4受体结合而起作用的。