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Role of Complement C5a/C3a agonists existing broadly in animals and plants

广泛存在于动物和植物中的补体 C5a/C3a 激动剂的作用

基本信息

批准号：
09660084
负责人：
YOSHIKAWA Masaaki
金额：
$ 2.18万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660084/
关键词：
complement C3a C5a peptide food protein casein albumin albutensin ヒストンヘモグロビン

项目摘要

Complement C3a which is released from the amino-terminus region of Complement C3 induces inflammation and contraction of smooth muscle. We found that Complement C3a shows central effects such as anti-analgesia and anti-amnesia. Low molecular weight C3a agonists we isolated from tryptic digests of casein, rice albumin, hemoglobin, serum albumin and histone have common sequence at their carboxyl termini, hydrophobic residue-X_1-Leu-X_2-Arg. These peptides might bind C3a receptor because the sequence is common to that at the carboxyl terminus of C3a. Similar peptides were found in the primary structure of some endogenous bioactive peptides. Only a part of such peptides might have' physiological significance because such peptides are found broadly not only in animals but also in plants.Complement C5a which is also released from the amino-terminus region of Complement C5 has potent biological activities common to those of C3a. Albutensin A, Ala-Phe-Lys-Ala-Trp-Ser-Leu-Ala-Arg, which is released from porcine serum albumin binds both C3a and C5a receptors. On the other hand, Phe-Lys-Asp-Cys-His-Leu-Ala-Arg, which is released from lactoferrin binds C5a receptor. The Lys at the 7th residue from the carboxyl terminus seems to be essential for C5a receptor affinity since the structure at the carboxyl terminus of C5a is Lys-Asp-Met-Gln-Leu-Gly-Arg. Thus, C3a and C5a agonists existing broadly in animal and plants. It is expected to use some of them as pharmaceutical drugs or foods to improve our health.

补体C3a是从补体C3的氨基末端区域释放出来的，可引起血管的炎症和收缩。我们发现补体C3a具有中枢性作用，如抗镇痛和抗健忘。我们从酪蛋白、大米白蛋白、血红蛋白、血清白蛋白和组蛋白的胰酶解液中分离得到的低分子C3a激动剂在其羧基末端具有共同的序列，疏水残基-X_1-Leu-X_2-Arg。这些多肽可能与C3a受体结合，因为该序列与C3a羧基末端的序列相同。在一些内源生物活性多肽的一级结构中也发现了类似的多肽。补体C5a也是从补体C5的氨基末端区域释放出来的，它具有与C3a相同的强大生物活性。猪血清白蛋白释放的Albutensin A，Ala-Phe-Lys-Ala-Trp-Ser-Leu-Ala-Arg与C3a和C5a受体结合。另一方面，乳铁蛋白释放的Phe-Lys-Asp-Cys-His-Leu-Ala-Arg与C5a受体结合。由于C5a羧基末端的结构是Lys-Asp-Met-Gln-Leu-Gly-Arg，C5a羧基末端的第7个残基上的Lys似乎对C5a受体的亲和力是必不可少的。因此，C3a和C5a激动剂广泛存在于动植物体内。它有望将其中一些用作药物或食品，以改善我们的健康。