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Exploitation of anti-alopecic and hair-growth promoting peptides

抗脱发促毛发生长肽的开发

基本信息

批准号：
12559005
负责人：
YOSHIKAWA Masaaki
金额：
$ 7.74万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

抗脱发或头发生长问题是重要的享受舒适的生活。特别是，癌症化疗引起的脱发是一个严重的问题，因为它损害了患者的生活质量。在这些情况下，需要开发抗脱发剂。大豆肽-4（soymetide-4）是一种来源于大豆（β-conglycinin）的免疫刺激肽，经口给药后，对抗癌药足叶乙甙（etoposide）诱导的大鼠脱发有明显的预防作用，其抗脱发作用是由细菌趋化肽fMLP受体介导的。虽然口服fMLP无效，但静脉给药可预防脱发。人fMLP受体有两种亚型，FPR（high affinity site）和FPRL 1（low affinity site）。FPRL 1-选择性肽MMK-1也可预防依托泊苷诱导的脱发，提示低亲和力位点的重要性。fMLP的抗脱发作用可被组胺H1受体拮抗剂吡拉宁和IL-1抑制剂Lys-D-Pro-Thr阻止，提示组胺和IL-1参与。吡咯烷二硫代氨基甲酸铵的抗脱发作用也被阻断，提示NF-κB的活化在fMLP的抗脱发作用中起重要作用。拓扑异构酶II抑制剂足叶乙甙（etoposide）诱导的毛囊细胞凋亡可能通过激活NF-κB而被抑制，从而发挥抗脱发作用。这些类似物可以在食物蛋白质的酶促降解物中发现，或者通过基因工程引入食物蛋白质中。