Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, Brazil.
Mestrado Profissional em Biotecnologia e Gestão da Inovação, Centro Universitário de Sete Lagoas, Sete Lagoas, 35701-242, Minas Gerais, Brazil.
Sci Rep. 2018 Oct 3;8(1):14739. doi: 10.1038/s41598-018-33133-3.
Scorpion sting envenoming impacts millions of people worldwide, with cardiac effects being one of the main causes of death on victims. Here we describe the first Ca channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts's nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide lacking pharmacological activity which was directed to the nucleus of specific cancer cell lines. This research identifies a novel subfamily of Ca active toxins and provides new insights into biotechnological applications of animal venoms.
蝎毒中毒影响全球数百万人，心脏效应是导致受害者死亡的主要原因之一。在这里，我们描述了 Tityus serrulatus（Ts）毒液中存在的第一种钙通道毒素，一种称为 CPP-Ts 的细胞穿透肽。我们表明 CPP-Ts 通过激活心肌细胞的核内 InsP3R 增加细胞内 Ca 释放，从而导致这些细胞的收缩频率增加。除了提出一种新型钙活性毒素亚家族外，我们还利用 CPP-Ts 的核靶向特性研究了其作为靶向癌细胞核的药物输送系统的潜在用途。为此，我们制备了一种缺乏药理活性的合成 CPP-Ts 亚肽，该亚肽靶向特定癌细胞系的细胞核。这项研究确定了一种新型钙活性毒素亚家族，并为动物毒液的生物技术应用提供了新的见解。
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