Pathophysiology Laboratory, Instituto Butantan, Av. Vital Brazil, 1500, Butantã, SP, 05503-900, Brazil.
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes, 1524, Butantã, SP, 05508-900, Brazil.
Sci Rep. 2021 Dec 9;11(1):23712. doi: 10.1038/s41598-021-02552-0.
The important pharmacological actions of Crotoxin (CTX) on macrophages, the main toxin in the venom of Crotalus durissus terrificus, and its important participation in the control of different pathophysiological processes, have been demonstrated. The biological activities performed by macrophages are related to signaling mediated by receptors expressed on the membrane surface of these cells or opening and closing of ion channels, generation of membrane curvature and pore formation. In the present work, the interaction of the CTX complex with the cell membrane of macrophages is studied, both using biological cells and synthetic lipid membranes to monitor structural alterations induced by the protein. Here we show that CTX can penetrate THP-1 cells and induce pores only in anionic lipid model membranes, suggesting that a possible access pathway for CTX to the cell is via lipids with anionic polar heads. Considering that the selectivity of the lipid composition varies in different tissues and organs of the human body, the thermostructural studies presented here are extremely important to open new investigations on the biological activities of CTX in different biological systems.
已证实，响尾蛇毒素（CTX）对巨噬细胞（Crotalus durissus terrificus 毒液中的主要毒素）具有重要的药理作用，其对不同病理生理过程的控制具有重要的参与作用。巨噬细胞发挥的生物学活性与这些细胞表面表达的受体介导的信号转导、离子通道的开放和关闭、膜曲率的产生以及孔形成有关。在本工作中，通过使用生物细胞和合成脂质膜，研究了 CTX 复合物与巨噬细胞膜的相互作用，以监测该蛋白诱导的结构变化。结果表明 CTX 可以穿透 THP-1 细胞，并仅在带负电荷的脂质模型膜中诱导形成孔道，这表明 CTX 进入细胞的可能途径是通过带有负电荷的极性头部的脂质。考虑到脂质组成的选择性在人体不同组织和器官中会发生变化，因此这里呈现的热结构研究对于在不同生物系统中开展 CTX 生物活性的新研究极为重要。
