MEMBRANE STRUCTURAL FUNCTIONAL PERTURBATIONS INDUCED BY GOSSYPOL - EFFECTS ON MEMBRANE ORDER, LIPOSOME PERMEABILITY, AND INSULIN-SENSITIVE HEXOSE-TRANSPORT
MEMBRANE STRUCTURAL FUNCTIONAL PERTURBATIONS INDUCED BY GOSSYPOL - EFFECTS ON MEMBRANE ORDER, LIPOSOME PERMEABILITY, AND INSULIN-SENSITIVE HEXOSE-TRANSPORT
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DOI：
10.1016/0006-2952(86)90426-0
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发表时间：
1986-10-01
影响因子：
5.8
通讯作者：
SAUERHEBER, RD
中科院分区：
文献类型：
--
作者：
DEPEYSTER, A;HYSLOP, PA;SAUERHEBER, RD
研究了棉酚对膜结构和膜相关功能的影响，以探索棉酚能够破坏细胞过程的可能原因，其中许多过程涉及细胞内和质膜。本文报道的实验测量了棉酚对膜序、通透性和己糖运输的影响。对I（12,3）硝基脂肪酸自旋标记单层脂质体的电子自旋共振（ESR）研究表明，暴露于0.05 ~ 4mM棉酚会导致极性校正序参数(S)的剂量依赖性增加，表明暴露于棉酚后自旋探针的运动自由度降低。这一观察结果与棉酚导致膜脂基质有序或“凝聚”的观点是一致的。棉酚诱导的磷脂酰胆碱：胆固醇脂质体的序参量变化取决于脂质体的组成。当棉酚：磷脂比增加到10摩尔%时，暴露于棉酚的脂质体对甘油的渗透性也增加。较高浓度的棉酚对增强渗透性的效果较差。此外，在37°棉酚孵育的新鲜分离大鼠脂肪细胞中，基础和胰岛素刺激的2-脱氧-d-[3H]葡萄糖转运受到抑制。在存在和不存在40 ng/ml胰岛素的情况下，大约在0.2 mM时出现半最大抑制。在低倍率（40倍）下对细胞的显微镜观察证实，己糖运输的减少不仅仅是由于脂肪细胞膜的破裂，导致完整细胞数量的减少和棉酚处理细胞中标签的积累减少。棉酚在测试浓度下对完整细胞的数量和大体形态没有显著的改变。我们认为，血浆和亚细胞膜脂质区域的有序性和通透性的增加可能有助于棉酚的一些毒性和药理学特性。我们的研究结果也支持了棉酚可能在对葡萄糖底物的能量代谢变化最敏感的细胞中发挥更明显的作用的观点。
The effects of gossypol on membrane structure and membrane-associated functions were studied to explore possible reasons for the ability of gossypol to disrupt cellular processes, many of which involve intracellular and plasma membranes. The experiments reported here measured the effects of gossypol on membrane order, permeability, and hexose transport. Electron spin resonance (ESR) studies of I(12,3) nitroxide fatty acid spin-labeled unilamellar liposomes showed that exposure to 0.05 to 4mM gossypol caused a dose-dependent increase in the polarity-corrected order parameter (S), indicating reduced motional freedom of the spin probe after exposure to gossypol. This observation is consistent with the idea that gossypol causes an ordering or “condensing” of the membrane lipid matrix. Gossypol-induced changes in order parameter in phosphatidylcholine:cholesterol liposomes varied depending on the liposome composition. Liposomes exposed to gossypol also showed increasing permeability to glycerol as the gossypol:phospholipid ratio increased up to 10 mole %. Higher concentrations of gossypol were less effective at enhancing permeability. In addition, basal and insulin-stimulated 2-deoxy-d-[3H]glucose transport were inhibited in freshly isolated rat adipocytes incubated with gossypol at 37°. Half-maximal inhibition occurred at approximately 0.2 mM for uptake in both the presence and absence of 40 ng/ml insulin. Microscopic observation of the cells under low power (40x) confirmed that diminished hexose transport was not simply due to breakage of the adipocyte plasma membrane, resulting in a decrease in intact cell population and decreased accumulation of label in the gossypol-treated cells. Gossypol produced no significant changes in numbers of intact cells or gross morphology at the concentrations tested. We suggest that ordering and increased permeability of the lipid regions of plasma and subcellular membranes may contribute to some of the toxic and pharmacologie properties of gossypol. Our results also support the idea that gossypol may exert more pronounced effects in cells that are most sensitive to variations in availability of glucose substrates for energy metabolism.