Characterization and functional analysis of cathelicidin-MH, a novel frog-derived peptide with anti-septicemic properties.

Characterization and functional analysis of cathelicidin-MH, a novel frog-derived peptide with anti-septicemic properties.
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具有抗败血症特性的新型青蛙衍生肽 cathelicidin-MH 的表征和功能分析

DOI:
10.7554/elife.64411
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发表时间:
2021-04-20
期刊:
影响因子:
7.7
通讯作者:
Xu X
Xu X
中科院分区:
生物学1区
文献类型:
--
作者:
Chai J;Chen X;Ye T;Zeng B;Zeng Q;Wu J;Kascakova B;Martins LA;Prudnikova T;Smatanova IK;Kotsyfakis M;Xu X

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抗菌肽是先天免疫反应的一部分,在宿主防御病原体中起着至关重要的作用。在这里,我们报道了一种新的抗菌肽,属于cathelicidin家族,cathelicidin- mh (cath-MH),从小hyla heymonsivogt蛙的皮肤。Cath-MH在模拟膜环境中具有单一α-螺旋结构,对真菌和细菌具有抗菌作用,特别是革兰氏阴性菌。与其他抗菌素相比,cath-MH通过影响组织纤溶酶原激活物、纤溶酶、β-胰蛋白酶、弹性酶、凝血酶和酶切酶的酶活性来抑制凝血。ath- mh具有抗脂多糖(LPS)和盲肠结扎以及穿刺性脓毒症的保护作用,通过其抗菌、LPS中和、凝血抑制作用以及抑制MAPK信号传导,有效改善多器官病理和炎症细胞因子。综上所述,这些数据表明cath-MH是治疗感染性休克的一种有吸引力的候选治疗剂。
Antimicrobial peptides form part of the innate immune response and play a vital role in host defense against pathogens. Here we report a new antimicrobial peptide belonging to the cathelicidin family, cathelicidin-MH (cath-MH), from the skin of Microhyla heymonsivogt frog. Cath-MH has a single α-helical structure in membrane-mimetic environments and is antimicrobial against fungi and bacteria, especially Gram-negative bacteria. In contrast to other cathelicidins, cath-MH suppresses coagulation by affecting the enzymatic activities of tissue plasminogen activator, plasmin, β-tryptase, elastase, thrombin, and chymase. Cath-MH protects against lipopolysaccharide (LPS)- and cecal ligation and puncture-induced sepsis, effectively ameliorating multiorgan pathology and inflammatory cytokine through its antimicrobial, LPS-neutralizing, coagulation suppressing effects as well as suppression of MAPK signaling. Taken together, these data suggest that cath-MH is an attractive candidate therapeutic agent for the treatment of septic shock.