Balogh Gábor, Horváth Ibolya, Nagy Enikõ, Hoyk Zsófia, Benkõ Sándor, Bensaude Olivier, Vígh László
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
FEBS J. 2005 Dec;272(23):6077-86. doi: 10.1111/j.1742-4658.2005.04999.x.
The concentrations of two structurally distinct membrane fluidizers, the local anesthetic benzyl alcohol (BA) and heptanol (HE), were used at concentrations so that their addition to K562 cells caused identical increases in the level of plasma membrane fluidity as tested by 1,6-diphenyl-1,3,5-hexatriene (DPH) anisotropy. The level of membrane fluidization induced by the chemical agents on isolated membranes at such concentrations corresponded to the membrane fluidity increase seen during a thermal shift up to 42 degrees C. The formation of isofluid membrane states in response to the administration of BA or HE resulted in almost identical downshifts in the temperature thresholds of the heat shock response, accompanied by increases in the expression of genes for stress proteins such as heat shock protein (HSP)-70 at the physiological temperature. Similarly to thermal stress, the exposure of the cells to these membrane fluidizers elicited nearly identical increases of cytosolic Ca2+ concentration in both Ca2+-containing and Ca2+-free media and also closely similar extents of increase in mitochondrial hyperpolarization. We obtained no evidence that the activation of heat shock protein expression by membrane fluidizers is induced by a protein-unfolding signal. We suggest, that the increase of fluidity in specific membrane domains, together with subsequent alterations in key cellular events are converted into signal(s) leading to activation of heat shock genes.
使用了两种结构不同的膜流动性促进剂，即局部麻醉剂苯甲醇（BA）和庚醇（HE），其浓度使得添加到K562细胞后，通过1,6 - 二苯基 - 1,3,5 - 己三烯（DPH）各向异性测试的质膜流动性水平出现相同程度的增加。在这样的浓度下，化学试剂在分离膜上诱导的膜流动性水平与热转移至42摄氏度期间观察到的膜流动性增加相对应。响应于BA或HE的施用而形成的等流动性膜状态导致热休克反应的温度阈值几乎相同程度的降低，同时在生理温度下应激蛋白如热休克蛋白（HSP）-70的基因表达增加。与热应激类似，将细胞暴露于这些膜流动性促进剂会在含钙和无钙培养基中引起几乎相同程度的胞质Ca2 +浓度增加，并且线粒体超极化的增加程度也非常相似。我们没有获得证据表明膜流动性促进剂对热休克蛋白表达的激活是由蛋白质解折叠信号诱导的。我们认为，特定膜结构域中流动性的增加，以及随后关键细胞事件的改变，被转化为导致热休克基因激活的信号。
