Ingolfsson Helgi I, Koeppe Roger E, Andersen Olaf S
Cornell/Rockefeller/Sloan-Kettering Tri-Institutional Program in Computational Biology & Medicine, New York, New York 10065, USA.
Biochemistry. 2007 Sep 11;46(36):10384-91. doi: 10.1021/bi701013n. Epub 2007 Aug 17.
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is the major bioactive compound in turmeric (Curcuma longa) with antioxidant, antiinflammatory, anticarcinogenic, and antimutagenic effects. At low muM concentrations, curcumin modulates many structurally and functionally unrelated proteins, including membrane proteins. Because the cell membranes' lipid bilayer serves as a gate-keeper and regulator of many cell functions, we explored whether curcumin modifies general bilayer properties using channels formed by gramicidin A (gA). gA channels form when two monomers from opposing monolayers associate to form a conducting dimer with a hydrophobic length that is less than the bilayer hydrophobic thickness; gA channel formation thus causes a local bilayer thinning. The energetic cost of this bilayer deformation alters the gA monomer <--> dimer equilibrium, which makes the channels' appearance rate and lifetime sensitive to changes in bilayer material properties, and the gA channels become probes for changes in bilayer properties. Curcumin decreases bilayer stiffness, increasing both gA channel lifetimes and appearance rates, meaning that the energetic cost of the gA-induced bilayer deformation is reduced. These results show that curcumin may exert some of its effects on a diverse range of membrane proteins through a bilayer-mediated mechanism.
姜黄素(1,7 - 双(4 - 羟基 - 3 - 甲氧基苯基)- 1,6 - 庚二烯 - 3,5 - 二酮)是姜黄(Curcuma longa)中的主要生物活性化合物,具有抗氧化、抗炎、抗癌和抗诱变作用。在低微摩尔浓度下,姜黄素可调节许多结构和功能不相关的蛋白质,包括膜蛋白。由于细胞膜的脂质双层充当许多细胞功能的守门人和调节器,我们研究了姜黄素是否通过短杆菌肽A(gA)形成的通道来改变脂质双层的一般性质。当来自相对单层的两个单体结合形成具有小于双层疏水厚度的疏水长度的导电二聚体时,gA通道形成;因此,gA通道的形成会导致局部双层变薄。这种双层变形的能量成本改变了gA单体<-->二聚体的平衡,这使得通道的出现率和寿命对双层材料性质的变化敏感,并且gA通道成为双层性质变化的探针。姜黄素降低了双层的刚度,增加了gA通道的寿命和出现率,这意味着gA诱导的双层变形的能量成本降低。这些结果表明,姜黄素可能通过双层介导的机制对多种膜蛋白发挥其某些作用。