Reyes J, Allen J, Tanphaichitr N, Bellvé A R, Benos D J
J Biol Chem. 1984 Aug 10;259(15):9607-15.
Gossypol, an aldehyde extracted from cotton plants, produces both general toxic and antifertility effects in mammals. The cellular mechanisms by which gossypol exerts these effects are not understood. In this study, we have characterized the interactions of gossypol with lipid monolayer and bilayer membranes in order to assess if the drug acts by modifying the electrochemical properties of membranes. The charged form of gossypol binds to monolayers of different lipid compositions with apparent dissociation constants ranging from 0.7 to 2 microM. Binding of charged gossypol decreases the interfacial potential by 80-235 mV, the magnitude of this decrease being dependent upon the lipid composition. Gossypol also induces a conductance in phospholipid bilayer membranes. The relation between steady-state bilayer conductance versus gossypol concentration indicates that the current-carrying species is a single molecule of gossypol. The increase in bilayer conductance is accompanied by an increase in proton permeability. These changes induced by gossypol in model membranes can account for the mitochondrial uncoupling effects of this molecule and may be responsible for the inhibitory effects of gossypol on several membrane transport systems.
棉酚是从棉花植株中提取的一种醛类物质，对哺乳动物具有一般毒性和抗生育作用。棉酚发挥这些作用的细胞机制尚不清楚。在本研究中，我们对棉酚与脂质单层膜和双层膜的相互作用进行了表征，以评估该药物是否通过改变膜的电化学性质起作用。带电荷形式的棉酚与不同脂质组成的单层膜结合，其表观解离常数范围为0.7至2微摩尔。带电荷的棉酚结合使界面电位降低80 - 235毫伏，这种降低的幅度取决于脂质组成。棉酚还能诱导磷脂双层膜的电导。稳态双层膜电导与棉酚浓度之间的关系表明，载流物质是单个棉酚分子。双层膜电导的增加伴随着质子渗透性的增加。棉酚在模型膜中引起的这些变化可以解释该分子的线粒体解偶联作用，并且可能是棉酚对几种膜转运系统产生抑制作用的原因。
