title: Differential effects induced by alpha- and beta-endosulfan in lipid bilayer organization are reflected in proton permeability.
abstract: The effects of two insecticides isomers, alpha- and beta-endosulfan, on the passive proton permeability of large unilamellar vesicles (LUV) reconstituted with dipalmitoylphosphatidylcholine (DPPC) or mitochondrial lipids were reported. In DPPC (LUV) gel phase, at 30 degrees C, the global kinetic constant (K) of proton permeability (proportional to the proton permeability) initially increased slightly with the increase of alpha-endosulfan/lipid molar ratio up to 0.143. In the range from 0.143 to 0.286, a discontinuity in the increment occurred and, above this range, the proton permeability increased substantially. In DPPC fluid phase, at 48 degrees C, the proton permeability showed a behavior identical to that observed in gel DPPC, with a sharp increase for alpha-endosulfan/lipid molar ratios ranging from 0.143 to 0.286. At these and higher concentrations, alpha-endosulfan induced phase separation in the plane of DPPC membranes, as revealed by differential scanning calorimetry (DSC). Conversely to alpha-endosulfan, beta-endosulfan induced only a slight increase in the proton permeability, either in the fluid or the gel phase of DPPC, for all beta-endosulfan/lipid molar ratios tested. Additionally, the effects of the endosulfan isomers on the proton permeability of mitochondrial fluid lipid dispersions, at 37 degrees C, are similar to those described for DPPC. The beta-isomer induced a very small effect, and alpha-endosulfan, at low concentrations, increased slightly the proton permeability, but for insecticide/lipid molar ratios above 0.143 the permeability increased substantially. Consequently, the membrane physical state of synthetic and native lipid dispersions, as affected by the structural features of alpha- and beta-endosulfan, influenced the proton permeability. The effects here observed in vitro suggest that the formation of lateral membrane domains may underlay the biological activity of alpha-endosulfan in vivo, contributing to its higher degree of toxicity as compared with beta-endosulfan.
authors.affiliation: Centro de Neurociências e Biologia Celular, Departamento de Zoologia, Universidade de Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Romeu A
authors.initials: RA
authors.lastname: Videira
authors.forename: Maria C
authors.initials: MC
authors.lastname: Antunes-Madeira
authors.forename: Vítor M C
authors.initials: VM
authors.lastname: Madeira
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D004726:Endosulfan / Q000737:chemistry / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated; D066298:In Vitro Techniques; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D007536:Isomerism; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D010539:Permeability / Q000187:drug effects; D011522:Protons; D013050:Spectrometry, Fluorescence
chemical_list: D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D008051:Lipid Bilayers; D008081:Liposomes; D011522:Protons; D015060:1,2-Dipalmitoylphosphatidylcholine; D004726:Endosulfan