环境化
毒液
生物
肾
蛇毒
药理学
分子生物学
生物化学
内分泌学
作者
Dilza Trevisan-Silva,Miguel Cosenza-Contreras,Úrsula Castro de Oliveira,Nancy da Rós,Débora Andrade-Silva,Milene C. Menezes,Ana Karina de Oliveira,Jaqueline Gomes Rosa,Ana Teresa Azevedo Sachetto,Martin L. Biniossek,Niko Pinter,Marcelo Larami Santoro,Milton Yutaka Nishiyama-Jr,Oliver Schilling,Solange M.T. Serrano
标识
DOI:10.1016/j.ijbiomac.2023.127279
摘要
Snakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after, respectively, 2 h and 6 h. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The mouse overall response underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.
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