-
抗菌肽是一种存在于各种生物体内的防御性多肽,是生物进化过程中留存的重要先天免疫组成部分[1]。鱼类是抗菌肽的重要来源之一,已被发现的鱼类抗菌肽已达上百种。Epinecidin-1抗菌肽于2006年首次从石斑鱼白细胞的cDNA文库被鉴定发现,其基因由3个内含子和4个外显子组成,编码一种由25个氨基酸(序列为FIFHIIKGLFHAGKMIHGLVTRRRH)组成的成熟抗菌肽。这种抗菌肽的分子量为2985.63,等电点为 12.31。Epinecidin-1抗菌肽属于piscidins 家族,具有两亲性的α-螺旋结构,两侧含有疏水和亲水残基,能破坏病原体细胞膜的完整性从而达到杀伤作用[2]。通常,Epinecidin-1抗菌肽mRNA在石斑鱼的各种器官组织中均能表达,尤其是在头肾、腮、皮肤等部位。在细菌脂多糖的刺激下,石斑鱼头肾内Epinecidin-1抗菌肽 mRNA的转录表达量显著增加,翻译出更多的Epinecidin-1抗菌肽用来抵御外来病原微生物的侵入[3]。
由于从生物样品中获得研究所需的大量抗菌肽相当困难,因此抗菌肽的化学合成已成为首选方法[4]。Epinecidin-1抗菌肽可以采用Fmoc固相多肽合成法制备获得,并通过反相高效液相色谱法与质谱法分别对其进行纯化与分析。与完整的Epinecidin-1抗菌肽相比,合成的21聚体Epinecidin-1抗菌肽也能保护鱼类免受感染,但总体活性较低。尽管如此,由于合成短肽更具成本效益,大多数研究还是选择21聚体Epinecidin-1抗菌肽,并在C端酰胺化,用以改善其抗菌活性[5]。合成的Epinecidin-1抗菌肽具有多种药理活性,包括抗病原微生物、免疫调节、抗癌、伤口愈合等,已被用于局部伤口的愈合治疗以及提高水产养殖鱼类的免疫力方面[6]。本文旨在介绍Epinecidin-1抗菌肽的作用机制、药理活性、局限性以及应用前景方面的研究进展,为进一步研究与应用提供借鉴。
Research progress on antibacterial peptides Epinecidin-1
-
摘要: Epinecidin-1抗菌肽是从石斑鱼中提取的一种小分子活性多肽,是其先天免疫防御系统抵抗各种病原体的第一道防线。体内外研究证实,Epinecidin-1抗菌肽不仅表现出广谱的抗病原体活性(包括细菌、真菌、病毒和寄生虫等),还具有免疫调节、抗癌以及伤口愈合等药理活性。归纳近年Epinecidin-1抗菌肽的有关研究,对该抗菌肽的作用机制、药理活性、潜在局限性及应用前景进行综述,为下一步研究提供依据。
-
关键词:
- 抗菌肽 /
- Epinecidin-1 /
- 作用机制
Abstract: The antimicrobial peptide Epinecidin-1 is a kind of small molecule active peptides extracted from Epinephelus coioides, which serves as the first line of defense for innate immune defense system of Epinephelus coioides against various pathogens. In vitro and in vivo studies have confirmed that the antimicrobial peptide Epinecidin-1 not only exhibits broad-spectrum anti-pathogen activities (including bacteria, fungi, viruses, and parasites, etc.), but also has pharmacological activities such as immune regulation, anti-cancer and wound healing. In this paper, the relevant research on the antimicrobial peptide Epinecidin-1 in recent years were summarized, including its mechanism of action, pharmacological activities, potential limitations and application prospects , so as to provide information for further research.-
Key words:
- antimicrobial peptides /
- Epinecidin-1 /
- mechanism
-
[1] SHABIR U, ALI S, MAGRAY A R, et al Fish antimicrobial peptides (AMP's) as essential and promising molecular therapeutic agents: a review[J]. Microb Pathog2018 114 50 56 .[2] YIN Z X, HE W, CHEN W J, et al . Cloning, expression and antimicrobial activity of an antimicrobial peptide, epinecidin-1, from the orange-spotted grouper, Epinephelus coioides[J]. Aquaculture2006 253 1-4 204 211 .[3] ZHUANG Z R, YANG X D, HUANG X Z, et al . Three new piscidins from orange-spotted grouper (Epinephelus coioides): Phylogeny, expression and functional characterization[J]. Fish Shellfish Immunol2017 66 240 253 .[4] HANEY E F, MANSOUR S C, HANCOCK R E W Antimicrobial peptides: an introduction[J]. Methods Mol Biol2017 1548 3 22 .[5] PAN C Y, CHEN J Y, CHENG Y S E, et al . Gene expression and localization of the epinecidin-1 antimicrobial peptide in the grouper (Epinephelus coioides), and its role in protecting fish against pathogenic infection[J]. DNA Cell Biol2007 26 6 403 413 .[6] CHEE P Y, MANG M, LAU E S, et al . Epinecidin-1, an antimicrobial peptide derived from grouper (Epinephelus coioides): pharmacological activities and applications[J]. Front Microbiol2019 10 2631 .[7] NARAYANA J L, HUANG H N, WU C J, et al . Epinecidin-1 antimicrobial activity: in vitro membrane Lysis and in vivo efficacy against Helicobacter pylori infection in a mouse model[J]. Biomaterials2015 61 41 51 .[8] 李云香, 姚倩, 任玫, 等 抗菌肽作用机制研究进展[J]. 动物医学进展2019 40 9 98 103 .[9] LEE S C, PAN C Y, CHEN J Y The antimicrobial peptide, epinecidin-1, mediates secretion of cytokines in the immune response to bacterial infection in mice[J]. Peptides2012 36 1 100 108 .[10] SU B C, CHEN J Y . Epinecidin-1: an orange-spotted grouper antimicrobial peptide that modulates Staphylococcus aureus lipoteichoic acid-induced inflammation in macrophage cells[J]. Fish Shellfish Immunol2020 99 362 367 .[11] HUANG X Z, HU B C, YANG X D, et al . The putative mature peptide of piscidin-1 modulates global transcriptional profile and proliferation of splenic lymphocytes in orange-spotted grouper (Epinephelus coioides)[J]. Fish Shellfish Immunol2019 86 1035 1043 .[12] HUANG T C, CHEN J Y Proteomic and functional analysis of zebrafish after administration of antimicrobial peptide epinecidin-1[J]. Fish Shellfish Immunol2013 34 2 593 598 .[13] HUANG H N, PAN C Y, SU B C, et al . Epinecidin-1 protects against methicillin resistant Staphylococcus aureus infection and Sepsis in pyemia pigs[J]. Mar Drugs2019 17 12 693 .[14] PAN C Y, CHEN J C, SHEEN J F, et al . Epinecidin-1 has immunomodulatory effects, facilitating its therapeutic use in a mouse model of Pseudomonas aeruginosa Sepsis[J]. Antimicrob Agents Chemother2014 58 8 4264 4274 .[15] CHEN J Y, PAN C Y. Use of epinecidin-1 peptides and anti-lipopolysaccharide factor peptides for treating microbial infection: US8377867[P]. 2013-02-19. [16] HUANG H N, PAN C Y, CHEN J Y . Grouper (Epinephelus coioides) antimicrobial peptide epinecidin-1 exhibits antiviral activity against foot-and-mouth disease virus in vitro[J]. Peptides2018 106 91 95 .[17] HUANG H N, PAN C Y, RAJANBABU V, et al Modulation of immune responses by the antimicrobial peptide, epinecidin (Epi)-1, and establishment of an Epi-1-based inactivated vaccine[J]. Biomaterials2011 32 14 3627 3636 .[18] HUANG H N, CHUANG C M, CHEN J Y, et al . Epinecidin-1: a marine fish antimicrobial peptide with therapeutic potential against Trichomonas vaginalis infection in mice[J]. Peptides2019 112 139 148 .[19] SU B C, LI C C, HORNG J L, et al Calcium-dependent calpain activation-mediated mitochondrial dysfunction and oxidative stress are required for cytotoxicity of epinecidin-1 in human synovial sarcoma SW982 cells[J]. Int J Mol Sci2020 21 6 2109 .[20] LUMPKINS K M, BOCHICCHIO G V, KELEDJIAN K, et al Glial fibrillary acidic protein is highly correlated with brain injury[J]. J Trauma2008 65 4 778 782 .[21] BATONI G, MAISETTA G, BRANCATISANO F L, et al Use of antimicrobial peptides against microbial biofilms: advantages and limits[J]. Curr Med Chem2011 18 2 256 279 .[22] BOLATCHIEV A . Antimicrobial peptides epinecidin-1 and beta-defesin-3 are effective against a broad spectrum of antibiotic-resistant bacterial isolates and increase survival rate in experimental Sepsis[J]. Antibiotics (Basel)2022 11 1 76 .[23] HUANG H N, RAJANBABU V, PAN C Y, et al Use of the antimicrobial peptide Epinecidin-1 to protect against MRSA infection in mice with skin injuries[J]. Biomaterials2013 34 38 10319 10327 .[24] SU B C, WU T H, HSU C H, et al . Distribution of positively charged amino acid residues in antimicrobial peptide epinecidin-1 is crucial for in vitro glioblastoma cytotoxicity and its underlying mechanisms[J]. Chem Biol Interact2020 315 108904 .[25] TING C H, CHEN Y C, CHEN J Y . Nile tilapia fry fed on antimicrobial peptide Epinecidin-1-expressing Artemia cyst exhibit enhanced immunity against acute bacterial infection[J]. Fish Shellfish Immunol, 2018, 81: 37-48.
计量
- 文章访问数: 3780
- HTML全文浏览量: 1328
- PDF下载量: 36
- 被引次数: 0