Vigh László, Horváth Ibolya, Maresca Bruno, Harwood John L
Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Hungary.
Trends Biochem Sci. 2007 Aug;32(8):357-63. doi: 10.1016/j.tibs.2007.06.009. Epub 2007 Jul 12.
In addition to high temperature, other stresses and clinical conditions such as cancer and diabetes can lead to the alteration of heat-shock protein (HSP) levels in cells. Moreover, HSPs can associate with either specific lipids or with areas of special membrane topology (such as lipid rafts), and changes in the physical state of cellular membranes can alter hsp gene expression. We propose that membrane microheterogeneity is important for regulating the HSP response. In support of this hypothesis, when particular membrane intercalating compounds are used to alter membrane properties, the simultaneous normalization of dysregulated expression of HSPs causes beneficial responses to disease states. Therefore, these compounds (such as hydroxylamine derivatives) have the potential to become a new class of pharmaceuticals for use in 'membrane-lipid therapy'.
除了高温外，其他应激因素以及癌症和糖尿病等临床病症也可导致细胞内热休克蛋白（HSP）水平的改变。此外，热休克蛋白可与特定脂质或特殊膜拓扑结构区域（如脂筏）相结合，细胞膜物理状态的变化可改变热休克蛋白基因的表达。我们认为膜微不均一性对于调节热休克蛋白反应很重要。为支持这一假说，当使用特定的膜插入化合物来改变膜特性时，热休克蛋白失调表达的同时正常化会对疾病状态产生有益反应。因此，这些化合物（如羟胺衍生物）有潜力成为用于“膜脂质疗法”的新型药物。
