Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
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DOI：
10.1074/jbc.m008922200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
Ganz, T
中科院分区：
文献类型：
--
作者：
Park, CH;Valore, EV;Ganz, T
富含半胱氨酸的抗菌肽广泛存在于动植物组织中，参与宿主的防御。在昆虫中，大多数是在脂肪体中合成的，脂肪体是一种类似于脊椎动物肝脏的器官。从人类尿液中，我们的特点是富含半胱氨酸的肽与三种形式不同的氨基末端截短，我们命名为hepcidin（Hepc），因为它的起源在肝脏和它的抗菌特性。两种主要形式，Hepc 20和Hepc 25，含有20和25个氨基酸残基，所有8个半胱氨酸通过分子内二硫键连接。反向翻译和数据库搜索发现了从鱼类到人类物种的同源肝脏cDNA和人类19号染色体上相应的人类基因组序列。通过5'端快速扩增cDNA末端的完整cDNA为0.4个酶对，与北方印迹上的hepcidin mRNA大小一致。肝脏是mRNA表达的主要部位。编码的前原肽含有84个氨基酸，但在尿液中仅发现20-25个氨基酸的加工形式。Hepcidins对白色念珠菌、烟曲霉和尼日尔曲霉具有抗真菌活性，对大肠杆菌、金黄色葡萄球菌、表皮葡萄球菌和B族链球菌具有抗菌活性。铁调素可能是在昆虫脂肪体中产生的富含半胱氨酸的抗微生物肽的脊椎动物对应物。
Cysteine-rich antimicrobial peptides are abundant in animal and plant tissues involved in host defense. In insects, most are synthesized in the fat body, an organ analogous to the liver of vertebrates. From human urine, we characterized a cysteine-rich peptide with three forms differing by amino-terminal truncation, and we named it hepcidin (Hepc) because of its origin in the liver and its antimicrobial properties. Two predominant forms, Hepc20 and Hepc25, contained 20 and 25 amino acid residues with all 8 cysteines connected by intramolecular disulfide bonds. Reverse translation and search of the data bases found homologous liver cDNAs in species from fish to human and a corresponding human genomic sequence on human chromosome 19. The full cDNA by 5' rapid amplification of cDNA ends was 0.4 kilobase pair, in agreement with hepcidin mRNA size on Northern blots. The liver was the predominant site of mRNA expression. The encoded prepropeptide contains 84 amino acids, but only the 20-25-amino acid processed forms were found in urine. Hepcidins exhibited antifungal activity against Candida albicans, Aspergillus fumigatus, and Aspergillus niger and antibacterial activity against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and group B Streptococcus. Hepcidin may be a vertebrate counterpart of cysteine-rich antimicrobial peptides produced in the fat body of insects.