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作 者:黄萍 孟庆泰 张凤民 HUANG Ping;MENG Qing-Tai;ZHANG Feng-Min(Department of Microbiology,WU Lien-Teh Institute,Harbin Medical University,Heilongjiang Provincial Key Laboratory of Immunity and Infection,Heilongjiang Provincial Key Laboratory of Pathogenic Biology,Harbin 150081,China)
机构地区:[1]哈尔滨医科大学医学微生物学教研室,哈尔滨医科大学伍连德研究所,黑龙江省免疫与感染重点实验室,黑龙江省普通高校病原生物学重点实验室,哈尔滨150081
出 处:《中国生物化学与分子生物学报》2023年第4期507-515,共9页Chinese Journal of Biochemistry and Molecular Biology
基 金:国家重点研发项目(No.2017YFB0403805);国家自然科学基金项目(No.81701573)资助。
摘 要:人核糖核酸酶A(human RNase A)超家族包含13个具有不同生物活性的成员(RNase 1~RNase 13),其蛋白质结构除具有催化保守序列外,还具有显著多样性的序列,决定了人类核糖核酸酶A可发挥核糖核酸酶活性之外的生物学功能。人核糖核酸酶A超家族成员在多种免疫细胞例如嗜酸性粒细胞、中性粒细胞、单核细胞和巨噬细胞中表达,并可被分泌以发挥多种多样的生物学功能,包括抗微生物活性、促进宿主防御、参与血管生成及精子成熟等。其中,人核糖核酸酶A超家族部分成员,可通过水解病毒RNA、抑制病毒复制、破坏细菌细胞壁、促进微生物凝集、损伤寄生虫细胞膜和线粒体膜等直接作用,以及通过宿主天然免疫细胞介导的间接作用,发挥抗微生物及寄生虫活性,参与宿主防御。本文对人核糖核酸酶A的抗微生物(包括病毒、细菌、真菌)和抗寄生虫活性及其作用机制进行综述,并对人核糖核酸酶A作为抗微生物活性物质和天然免疫分子,用于治疗严重和耐药微生物感染的前景进行展望。Human RNase A(human RNase A)superfamily contains 13 members(RNase 1~RNase 13)with different biological activities.In addition to the conserved catalytic sequence,its protein structure also has a significant diversity of sequences,which determines that human ribonuclease A can exert biological functions other than ribonuclease activity.Human RNase A superfamily members are expressed in various immune cells such as eosinophils,neutrophils,monocytes,and macrophages and can be secreted to exert various biological functions,including anti-microbial activity,promote host defense,participate in angiogenesis and sperm maturation,etc.Some members of the human ribonuclease A superfamily can exert antimicrobial and antiparasitic activities through direct actions such as hydrolysis of viral RNA,inhibition of viral replication,destruction of bacterial cell walls,promotion of microbial aggregation,damage to parasitic cell membranes and mitochondrial membranes,and indirect actions mediated by host innate immune cells,thereby participating in host defense.This article reviews the antimicrobial(including viruses,bacteria,and fungi)and antiparasitic activities of human ribonuclease A and their mechanisms of action.It also prospects the prospects of human ribonuclease A as an active antimicrobial substance and innate immune molecule for the treatment of severe and drug-resistant microbial infections.
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