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蛋白质组学鉴定和定量蛇毒生物标志物在毒液和血浆细胞外囊泡中的研究

Proteomic Identification and Quantification of Snake Venom Biomarkers in Venom and Plasma Extracellular Vesicles.

机构信息

National Natural Toxins Research Center (NNTRC), Texas A&M University-Kingsville, MSC 224, 975 West Avenue B, Kingsville, TX 78363, USA.

Department of Chemistry, Texas A&M University-Kingsville, MSC 161, Kingsville, TX 78363, USA.

出版信息

Toxins (Basel). 2021 Sep 15;13(9):654. doi: 10.3390/toxins13090654.

DOI:10.3390/toxins13090654
PMID:34564658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8473211/
Abstract

The global exploration of snakebites requires the use of quantitative omics approaches to characterize snake venom as it enters into the systemic circulation. These omics approaches give insights into the venom proteome, but a further exploration is warranted to analyze the venom-reactome for the identification of snake venom biomarkers. The recent discovery of extracellular vesicles (EVs), and their critical cellular functions, has presented them as intriguing sources for biomarker discovery and disease diagnosis. Herein, we purified EV's from the snake venom (svEVs) of and , and from plasma of BALB/c mice injected with venom from each snake using EVtrap in conjunction with quantitative mass spectrometry for the proteomic identification and quantification of svEVs and plasma biomarkers. Snake venom EVs from and were highly enriched in 5' nucleosidase, L-amino acid oxidase, and metalloproteinases. In mouse plasma EVs, a bioinformatic analysis for revealed upregulated responses involved with cytochrome P450, lipid metabolism, acute phase inflammation immune, and heat shock responses, while downregulated proteins were associated with mitochondrial electron transport, NADH, TCA, cortical cytoskeleton, reticulum stress, and oxidative reduction. Altogether, this analysis will provide direct evidence for svEVs composition and observation of the physiological changes of an envenomated organism.

摘要

全球范围内对蛇伤的研究需要采用定量组学方法来描述蛇毒进入体循环后的特征。这些组学方法可以深入了解蛇毒的蛋白质组，但为了分析蛇毒反应组以鉴定蛇毒生物标志物，还需要进一步探索。最近发现的细胞外囊泡（EVs）及其关键的细胞功能，使它们成为生物标志物发现和疾病诊断的有趣来源。在此，我们使用 EVtrap 从小（）和（）蛇的蛇毒液中以及从每种蛇毒液注射到 BALB/c 小鼠的血浆中纯化 EVs（svEVs），并使用定量质谱法对 svEVs 和血浆生物标志物进行蛋白质组学鉴定和定量分析。 和 的蛇毒 EVs 中富含 5'核苷酸酶、L-氨基酸氧化酶和金属蛋白酶。在小鼠血浆 EVs 中，生物信息学分析表明，与细胞色素 P450、脂质代谢、急性期炎症免疫和热休克反应相关的上调反应，而下调蛋白与线粒体电子传递、NADH、TCA、皮质细胞骨架、内质网应激和氧化还原有关。总之，这项分析将为 svEVs 的组成提供直接证据，并观察到被蛇咬伤的生物体的生理变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/3b40537f5f0c/toxins-13-00654-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/e84fc42cd3a5/toxins-13-00654-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/3144eeb6b46e/toxins-13-00654-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/3b40537f5f0c/toxins-13-00654-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/e84fc42cd3a5/toxins-13-00654-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/755c074d83b5/toxins-13-00654-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/0c9791023634/toxins-13-00654-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/85f67b1212c2/toxins-13-00654-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/83ff3f57c191/toxins-13-00654-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc56/8473211/67adc5032a1d/toxins-13-00654-g007.jpg
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