据赖仞研究团队的博士研究生刘存宝介绍,以前发现的两大类皮肤抗氧化系统,一类为基因编码的大分子抗氧化酶类,如超氧化物歧化酶(SOD);另一类为小分子有机物,如维生素。而两栖类动物是如何在阳光下富含氧气的空气环境中保持其裸露皮肤免受自由基的伤害,不论从进化的角度或对动物皮肤生物学感兴趣的研究者来说,都是个很重要和有趣的问题。而关于这种防护机制的肽类系统研究尚待完善。
在此基础上,该研究团队从多肽类抗氧化系统对自由基的清除效率、速度以及作用机理进行了深入研究。他们从一种名叫大绿蛙的皮肤中新发现了名为antioxidin-RL的抗氧化小肽,这为抗氧化肽系统在两栖类动物皮肤中可能广泛存在提供了佐证。antioxidin-RL具有强大的自由基清除能力,可在2秒钟内清除一种名为ABTS的自由基的80%,比目前广泛商业使用的抗氧化剂(如2,6-二叔丁基-4-甲基苯酚和维生素E)快约2~4倍,表明以antioxindin为代表的抗氧化肽类系统可能在保持两栖类动物皮肤的氧化还原反应平衡中扮演重要角色。同时,通过氨基酸突变、核磁共振实验和其他一系列生化试验证明,此小肽中位于第十位的半胱氨酸残基在其快速清除自由基的能力中扮演重要角色,而其中的酪氨酸则在小肽结合自由基的过程中起作用。
目前,该研究结果发表在美国自由基生物医学联合会会刊Free Radical Biology & Medicine上,相关成果已经申请发明专利“大绿蛙抗氧化肽antioxidin-RL及其基因和应用”。该发明对生物医学及化妆品研发具有重要意义。
原文出处:
Free Radical Biology and Medicine doi:10.1016/j.freeradbiomed.2010.01.036
Frog skins keep redox homeostasis by antioxidant peptides with rapid radical scavenging ability
Cunbao Liua, b, 1, Jing Hongb, c, 1, Hailong Yanga, b, 1, Jing Wua, b, Dongying Maa, b, Dongsheng Lia, Donghai Linc, , and Ren Laia, d, ,
a Biotoxin Unit of the Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
b Graduate School, Chinese Academy of Sciences, Beijing, China
c Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
d Key Laboratory of Microbiological Engineering of the Agricultural Environment, Ministry of Agriculture, Life Sciences College, Nanjing Agricultural University, Nanjing, Jiangsu, China
The question of how amphibians can protect themselves from reactive oxygen species when exposed to the sun in an oxygen-rich atmosphere is important and interesting, not only from an evolutionary viewpoint, but also as a primer for researchers interested in mammalian skin biology, in which such peptide systems for antioxidant defense are not well studied. The identification of an antioxidant peptide named antioxidin-RL from frog (Odorrana livida) skin in this report supports the idea that a peptide antioxidant system may be a widespread antioxidant strategy among amphibian skins. Its ability to eliminate most of the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical tested within 2 s, which is much faster than the commercial antioxidant factor butylated hydroxytoluene, suggests that it has a potentially large impact on redox homeostasis in amphibian skins. Cys10 is proven to be responsible for its rapid radical scavenging function and tyrosines take part in the binding of antioxidin-RL to radicals according to our nuclear magnetic resonance assay.