Vogel P, Dux E, Wiessner C
Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Cologne, Germany.
Metab Brain Dis. 1997 Sep;12(3):203-17.
In this study the effects of 30 min heat-shock, ranging from 42 degrees C to 46 degrees C, on survival, protein synthesis and HSP72 expression were investigated in primary rat neuronal cultures. Heat-shock of 44 degrees C resulted in a complete, but transient inhibition of protein synthesis which recovered within 24 h. 46 degrees C heat-shock resulted in an irreversible inhibition of protein synthesis and complete neuronal loss within 24 h. Cycloheximide treatment of neuronal cultures resulted in aggravation of neuronal cell damage after heat-shock of 44 degrees C, indicating that the capacity for recovery of the overall protein synthesis is an important survival factor. In addition, the reduction of neuronal cell damage mediated by heat conditioning was abolished by cycloheximide treatment, indicating that the function of new proteins is important for induced thermotolerance. Induction of the strictly inducible member of the heat-shock protein 70kDa family, HSP72, was found in those few astrocytes which were contaminating the neuronal cell cultures, but not in neurons. These results indicate that newly synthesised proteins other than HSP72 are likely to mediate neuronal protection following heat shock in our experiments. These findings raise the possibility that induced tolerance may not necessarily be mediated by HSP72.
在本研究中，我们在原代大鼠神经元培养物中研究了42℃至46℃范围内30分钟热休克对细胞存活、蛋白质合成及HSP72表达的影响。44℃热休克导致蛋白质合成完全但短暂的抑制，24小时内恢复。46℃热休克导致蛋白质合成不可逆抑制，并在24小时内导致神经元完全丧失。用环己酰亚胺处理神经元培养物，导致44℃热休克后神经元细胞损伤加重，这表明总体蛋白质合成的恢复能力是一个重要的存活因素。此外，环己酰亚胺处理消除了热预处理介导的神经元细胞损伤的减轻，这表明新蛋白质的功能对诱导耐热性很重要。在污染神经元细胞培养物的少数星形胶质细胞中发现了热休克蛋白70kDa家族严格诱导成员HSP72的诱导，但在神经元中未发现。这些结果表明，在我们的实验中，除HSP72外，新合成的蛋白质可能介导热休克后的神经元保护。这些发现增加了诱导耐受性不一定由HSP72介导的可能性。
