The lipid-mediated hypothesis of fumonisin B1 toxicodynamics tested in model membranes.
The disruption of lipidic metabolism was considered a good candidate to explain FB1 toxicity mechanism. In the present work we investigated molecular organizational changes induced by FB1-biomembrane interaction possibly involved in mycotoxic effects. FB1 was self-aggregated with a critical micellar concentration of 1.97 mM. FB1 (0-81.4 microM), decreased in a dose-dependent manner, the fluorescence anisotropy of TMA-DPH (from 0.349+/-0.003 to 0.1720+/-0.0035) in dpPC bilayers, whilst no differences were registered with DPH. At 5.6 microM in the subphase, FB1 increased the lateral surface pressure (pi) of a Langmuir film to an extent that depended on the monolayer composition (Deltapi dpPC:DOTAP 3:1>Deltapi dpPC:dpPA3:1>Deltapi dpPC), the molecular packing (Deltapi decreased linearly as a function of the initial pi) and the subphase pH (Deltapi pH 2.6>Deltapi pH 7.4 and maximal pi allowing the drug penetration pi cut-off was 34.3 and 27.7 mN/m at pH 2.63 and 7.4, respectively). FB1 increased the surface potential of dpPC and dpPC:DOTAP monolayers and decreased that of dpPC:dpPA. This suggested that FB1 acquired different orientations and/or foldings depending on the surface electrostatics and the toxin charge state. Moreover, FB1-lipid interactions were transduced into long-range effects at the mesoscopic level affecting the lipidic self-separated lateral domains shape and density.
Theumer
Martín G
MG
Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.
Clop
Eduardo M
EM
Rubinstein
Héctor R
HR
Perillo
María A
MA
D000818:Animals; D001665:Binding Sites; D037341:Fumonisins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology* / Q000633:toxicity; D008567:Membranes, Artificial; D008954:Models, Biological; D008968:Molecular Conformation; D009183:Mycotoxins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity
D037341:Fumonisins; D008055:Lipids; D008567:Membranes, Artificial; D009183:Mycotoxins; C056933:fumonisin B1