{"title":"从蝰蛇毒液中纯化的蛋白质和多肽的生物化学和毒理学","authors":"Jüri Siigur PhD, Ene Siigur PhD","doi":"10.1016/j.toxcx.2022.100131","DOIUrl":null,"url":null,"abstract":"<div><p>The isolation and characterization of individual snake venom components is important for a deeper understanding of the pathophysiology of envenomation and for improving the therapeutic procedures of patients. It also opens possibilities for the discovery of novel toxins that might be useful as tools for understanding cellular and molecular processes. The variable venom composition, toxicological and immunological properties of the common vipers (<em>Vipera berus berus</em>) have been reviewed. The combination of venom gland transcriptomics, bottom-up and top-down proteomics enabled comparison of common viper venom proteomes from multiple individuals. <em>V. b. berus</em> venom contains proteins and peptides belonging to 10–15 toxin families: snake venom metalloproteinase, phospholipases A<sub>2</sub> (PLA<sub>2</sub>), snake venom serine proteinase, aspartic protease, L-amino acid oxidase (LAAO), hyaluronidase, 5′-nucleotidase, glutaminyl-peptide cyclotransferase, disintegrin, C-type lectin (snaclec), nerve growth factor, Kunitz type serine protease inhibitor, snake venom vascular endothelial growth factor, cysteine-rich secretory protein, bradykinin potentiating peptide, natriuretic peptides. PLA<sub>2</sub> and LAAO from <em>V. b. berus</em> venom produce more pronounced cytotoxic effects in cancer cells than normal cells, via induction of apoptosis, cell cycle arrest and suppression of proliferation. Proteomic data of <em>V. b. berus</em> venoms from different parts of Russia and Slovakian Republic have been compared with analogous data for <em>Vipera nikolskii</em> venom. Proteomic studies demonstrated quantitative differences in the composition of <em>V. b. berus</em> venom from different geographical regions. Differences in the venom composition of <em>V. berus</em> were mainly driven by the age, sex, habitat and diet of the snakes. The venom variability of <em>V. berus</em> results in a loss of antivenom efficacy against snakebites. The effectiveness of antibodies is discussed. This review presents an overview with a special focus on different toxins that have been isolated and characterized from the venoms of <em>V. b. berus.</em> Their main biochemical properties and toxic actions are described.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171022000418/pdfft?md5=313a818676ab059a339a90b421792643&pid=1-s2.0-S2590171022000418-main.pdf","citationCount":"4","resultStr":"{\"title\":\"Biochemistry and toxicology of proteins and peptides purified from the venom of Vipera berus berus\",\"authors\":\"Jüri Siigur PhD, Ene Siigur PhD\",\"doi\":\"10.1016/j.toxcx.2022.100131\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The isolation and characterization of individual snake venom components is important for a deeper understanding of the pathophysiology of envenomation and for improving the therapeutic procedures of patients. It also opens possibilities for the discovery of novel toxins that might be useful as tools for understanding cellular and molecular processes. The variable venom composition, toxicological and immunological properties of the common vipers (<em>Vipera berus berus</em>) have been reviewed. The combination of venom gland transcriptomics, bottom-up and top-down proteomics enabled comparison of common viper venom proteomes from multiple individuals. <em>V. b. berus</em> venom contains proteins and peptides belonging to 10–15 toxin families: snake venom metalloproteinase, phospholipases A<sub>2</sub> (PLA<sub>2</sub>), snake venom serine proteinase, aspartic protease, L-amino acid oxidase (LAAO), hyaluronidase, 5′-nucleotidase, glutaminyl-peptide cyclotransferase, disintegrin, C-type lectin (snaclec), nerve growth factor, Kunitz type serine protease inhibitor, snake venom vascular endothelial growth factor, cysteine-rich secretory protein, bradykinin potentiating peptide, natriuretic peptides. PLA<sub>2</sub> and LAAO from <em>V. b. berus</em> venom produce more pronounced cytotoxic effects in cancer cells than normal cells, via induction of apoptosis, cell cycle arrest and suppression of proliferation. Proteomic data of <em>V. b. berus</em> venoms from different parts of Russia and Slovakian Republic have been compared with analogous data for <em>Vipera nikolskii</em> venom. Proteomic studies demonstrated quantitative differences in the composition of <em>V. b. berus</em> venom from different geographical regions. Differences in the venom composition of <em>V. berus</em> were mainly driven by the age, sex, habitat and diet of the snakes. The venom variability of <em>V. berus</em> results in a loss of antivenom efficacy against snakebites. The effectiveness of antibodies is discussed. This review presents an overview with a special focus on different toxins that have been isolated and characterized from the venoms of <em>V. b. berus.</em> Their main biochemical properties and toxic actions are described.</p></div>\",\"PeriodicalId\":37124,\"journal\":{\"name\":\"Toxicon: X\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2022-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2590171022000418/pdfft?md5=313a818676ab059a339a90b421792643&pid=1-s2.0-S2590171022000418-main.pdf\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicon: X\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590171022000418\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon: X","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590171022000418","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 4
摘要
单个蛇毒成分的分离和表征对于更深入地了解中毒的病理生理学和改善患者的治疗程序是重要的。它也为发现新的毒素提供了可能,这些毒素可能是理解细胞和分子过程的有用工具。综述了常见毒蛇(Vipera berus berus)的不同毒液组成、毒理学和免疫学特性。结合毒液腺转录组学,自下而上和自上而下的蛋白质组学,可以比较来自多个个体的常见毒蛇毒液蛋白质组学。V. b. berus毒液含有10-15个毒素科的蛋白质和多肽:蛇毒金属蛋白酶、磷脂酶A2 (PLA2)、蛇毒丝氨酸蛋白酶、天冬氨酸蛋白酶、l-氨基酸氧化酶(LAAO)、透明质酸酶、5′-核苷酸酶、谷氨酰胺肽环转移酶、分解素、c型凝集素(snaclec)、神经生长因子、库尼茨型丝氨酸蛋白酶抑制剂、蛇毒血管内皮生长因子、富半胱氨酸分泌蛋白、缓动肽增强肽、利钠肽。与正常细胞相比,来自白毒弧菌毒液的PLA2和LAAO通过诱导细胞凋亡、细胞周期阻滞和抑制增殖,对癌细胞产生更明显的细胞毒性作用。对来自俄罗斯和斯洛伐克共和国不同地区的贝鲁斯蝰蛇毒液的蛋白质组学数据与类似的尼古斯基蝰蛇毒液的数据进行了比较。蛋白质组学研究表明,来自不同地理区域的贝氏弧菌毒液组成在数量上存在差异。不同年龄、性别、生境和食性对青蛇毒液组成的影响较大。V. berus的毒液变异性导致抗蛇毒血清对蛇咬伤的功效丧失。讨论了抗体的有效性。这篇综述提出了一个概述,特别侧重于不同的毒素,已分离和特征的V. b. berus毒液。介绍了它们的主要生化特性和毒性作用。
Biochemistry and toxicology of proteins and peptides purified from the venom of Vipera berus berus
The isolation and characterization of individual snake venom components is important for a deeper understanding of the pathophysiology of envenomation and for improving the therapeutic procedures of patients. It also opens possibilities for the discovery of novel toxins that might be useful as tools for understanding cellular and molecular processes. The variable venom composition, toxicological and immunological properties of the common vipers (Vipera berus berus) have been reviewed. The combination of venom gland transcriptomics, bottom-up and top-down proteomics enabled comparison of common viper venom proteomes from multiple individuals. V. b. berus venom contains proteins and peptides belonging to 10–15 toxin families: snake venom metalloproteinase, phospholipases A2 (PLA2), snake venom serine proteinase, aspartic protease, L-amino acid oxidase (LAAO), hyaluronidase, 5′-nucleotidase, glutaminyl-peptide cyclotransferase, disintegrin, C-type lectin (snaclec), nerve growth factor, Kunitz type serine protease inhibitor, snake venom vascular endothelial growth factor, cysteine-rich secretory protein, bradykinin potentiating peptide, natriuretic peptides. PLA2 and LAAO from V. b. berus venom produce more pronounced cytotoxic effects in cancer cells than normal cells, via induction of apoptosis, cell cycle arrest and suppression of proliferation. Proteomic data of V. b. berus venoms from different parts of Russia and Slovakian Republic have been compared with analogous data for Vipera nikolskii venom. Proteomic studies demonstrated quantitative differences in the composition of V. b. berus venom from different geographical regions. Differences in the venom composition of V. berus were mainly driven by the age, sex, habitat and diet of the snakes. The venom variability of V. berus results in a loss of antivenom efficacy against snakebites. The effectiveness of antibodies is discussed. This review presents an overview with a special focus on different toxins that have been isolated and characterized from the venoms of V. b. berus. Their main biochemical properties and toxic actions are described.