Takahashi Ryoya, Toyoda Emi, Aoki Yasunobu, Suzuki Kazuo T, Goto Sataro
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Mech Ageing Dev. 2002 Nov;123(12):1605-15. doi: 10.1016/s0047-6374(02)00096-9.
The ability of hepatocytes isolated from young (7-10 months) and old (31 months) male F344/Jcl and F344/DuCrj rats to express heat shock protein (hsp) 27, hsp70 and hsp90 was determined after a mild heat shock (42.5 degrees C for 30 min). The induction of these three mRNA levels by the heat shock was 50-80% lower in hepatocytes isolated from old F344/Jcl rats than in those from young rats. However, the hepatocytes from old F344/DuCrj showed a marked increase (200-250%) in the induction of hsp mRNAs by heat shock when compared to cells from young rats. Because heat shock transcription factor (HSF) plays a critical role in regulating the transcription of hsp genes, the effect of age on the binding activity HSF to heat shock element (HSE) was also studied. Again, the induction of binding activity of HSF to HSE was significantly increased with age in hepatocytes from F344/DuCrj rats while the reverse was true for the cells from F344/Jcl. The induced levels of hsp mRNAs were positively correlated with the binding activity of HSF to HSE in hepatocyte extracts from both F344 substrains, suggesting that the diverse age-related changes of heat-shock response in F344 substrains occurs in HSF activity. The contradictory age-related change in the heat-shock response is discussed with the differences in biochemical and genetic properties of substrains of F344 rats.
在轻度热休克（42.5℃，30分钟）后，测定了从年轻（7 - 10个月）和老年（31个月）雄性F344/Jcl和F344/DuCrj大鼠分离的肝细胞表达热休克蛋白（hsp）27、hsp70和hsp90的能力。与年轻大鼠分离的肝细胞相比，从老年F344/Jcl大鼠分离的肝细胞中，热休克诱导的这三种mRNA水平降低了50 - 80%。然而，与年轻大鼠的细胞相比，老年F344/DuCrj大鼠的肝细胞在热休克诱导hsp mRNA方面显著增加（200 - 250%）。由于热休克转录因子（HSF）在调节hsp基因转录中起关键作用，因此还研究了年龄对HSF与热休克元件（HSE）结合活性的影响。同样，F344/DuCrj大鼠肝细胞中HSF与HSE的结合活性诱导随着年龄显著增加，而F344/Jcl大鼠的细胞则相反。在两个F344亚系的肝细胞提取物中，hsp mRNA的诱导水平与HSF与HSE的结合活性呈正相关，这表明F344亚系中与年龄相关的热休克反应的不同变化发生在HSF活性中。结合F344大鼠亚系生化和遗传特性的差异，讨论了与年龄相关的热休克反应的矛盾变化。
