Videira Romeu A, Antunes-Madeira Maria C, Madeira Vítor M C
Centro de Neurociências e Biologia Celular, Departamento de Zoologia, Universidade de Coimbra, 3004-517 Coimbra, Portugal.
Biochim Biophys Acta. 2002 Aug 19;1564(1):140-8. doi: 10.1016/s0005-2736(02)00441-8.
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.
报道了两种杀虫剂异构体，即α-硫丹和β-硫丹，对用二棕榈酰磷脂酰胆碱（DPPC）或线粒体脂质重构的大单层囊泡（LUV）的被动质子渗透性的影响。在30℃的DPPC（LUV）凝胶相中，质子渗透性的整体动力学常数（K）（与质子渗透性成正比）最初随着α-硫丹/脂质摩尔比增加到0.143而略有增加。在0.143至0.286范围内，增量出现不连续，在此范围之上，质子渗透性大幅增加。在48℃的DPPC流体相中，质子渗透性表现出与在凝胶DPPC中观察到的相同行为，对于α-硫丹/脂质摩尔比在0.143至0.286范围内急剧增加。在这些浓度及更高浓度下，差示扫描量热法（DSC）显示α-硫丹在DPPC膜平面内诱导相分离。与α-硫丹相反，对于所有测试的β-硫丹/脂质摩尔比，β-硫丹在DPPC的流体相或凝胶相中仅引起质子渗透性的轻微增加。此外，在37℃下，硫丹异构体对线粒体流体脂质分散体质子渗透性的影响与DPPC的情况相似。β-异构体引起的影响非常小，而低浓度的α-硫丹使质子渗透性略有增加，但对于高于0.143的杀虫剂/脂质摩尔比，渗透性大幅增加。因此，受α-硫丹和β-硫丹结构特征影响的合成和天然脂质分散体的膜物理状态影响了质子渗透性。此处体外观察到的结果表明，侧膜结构域的形成可能是α-硫丹体内生物活性的基础，这有助于其与β-硫丹相比具有更高的毒性。
