Wang S, Longo F M, Chen J, Butman M, Graham S H, Haglid K G, Sharp F R
Department of Neurology (V127), University of California, San Francisco.
Neurochem Int. 1993 Dec;23(6):575-82. doi: 10.1016/0197-0186(93)90106-f.
Specific probes were obtained using PCR cloning from rat brain for the 78 kDa glucose regulated (grp78), inducible 72 kDa (hsp70) as well as constitutive 73 kDa (hsc73) heat shock mRNAs. Grp78 and hsc73 were expressed in normal rat brain whereas hsp70 was not. Subcutaneous injection kainic acid (10 mg/kg) produced seizures and induced all three mRNAs. The induction of grp78 and hsp70 mRNAs occurred within 2 h, peaked between 6-8 h, persisted for 48 h, and returned to control levels by 72 h. Expression of the grp78 and hsp70 mRNAs after focal ischemia progressively increased with occlusion durations from 15-120 min in the cerebral cortex. Though grp78 and hsp70 mRNAs were induced modestly in the striatum by 15 min of ischemia, longer durations of ischemia were characterized by little change in the grp78 mRNA levels and relatively lower levels of hsp70 expression. This result indicates that progressive increases in the duration of ischemia in brain, prior to infarction, may produce proportional increases in transcription of the heat shock genes. However, once the duration of ischemia is long enough to produce infarction, this severely limits the availability of ATP which blocks transcription of the heat shock genes. In conclusion, concurrent induction of the heat shock genes suggests that kainic acid seizures and focal ischemia induce several different stress responses in brain cells caused by denaturation of proteins, changes of protein synthesis, and changes of protein glycosylation.
通过PCR克隆从大鼠脑中获得了特异性探针，用于检测78 kDa葡萄糖调节蛋白（grp78）、诱导型72 kDa（hsp70）以及组成型73 kDa（hsc73）热休克mRNA。Grp78和hsc73在正常大鼠脑中表达，而hsp70不表达。皮下注射海藻酸（10 mg/kg）引发癫痫发作并诱导所有三种mRNA表达。Grp78和hsp70 mRNA的诱导在2小时内发生，在6 - 8小时达到峰值，持续48小时，并在72小时恢复到对照水平。在大脑皮层，局灶性缺血后grp78和hsp70 mRNA的表达随着闭塞时间从15 - 120分钟逐渐增加。虽然缺血15分钟时grp78和hsp70 mRNA在纹状体中被适度诱导，但缺血时间延长时，grp78 mRNA水平变化不大，hsp70表达水平相对较低。这一结果表明，在梗死前脑缺血持续时间的逐渐增加可能会使热休克基因的转录成比例增加。然而，一旦缺血持续时间足够长导致梗死，这将严重限制ATP的可用性，从而阻断热休克基因的转录。总之，热休克基因的同时诱导表明，海藻酸癫痫发作和局灶性缺血在脑细胞中诱导了由蛋白质变性、蛋白质合成变化和蛋白质糖基化变化引起的几种不同应激反应。
