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Abstract
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.
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1 Instituto Butantan, Pathophysiology Laboratory, Butantã, Brazil (GRID:grid.418514.d) (ISNI:0000 0001 1702 8585); University of São Paulo, Department of Pharmacology, Institute of Biomedical Sciences, Butantã, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
2 University of São Paulo, Institute of Physics, Butantã, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
3 Technology-Based Business Incubator of São Paulo IPEN/USP – Cietec, Alchemy Inovação, Pesquisa e Desenvolvimento Ltda., Butantã, Brazil (GRID:grid.466806.a) (ISNI:0000 0001 2104 465X)
4 Paulista State University, Department of Biophysics and Pharmacology, Institute of Biosciences, Botucatu, Brazil (GRID:grid.410543.7) (ISNI:0000 0001 2188 478X)