Luce M C, Cristofalo V J
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Exp Cell Res. 1992 Sep;202(1):9-16. doi: 10.1016/0014-4827(92)90398-r.
The expression of three major classes of heat shock genes was examined in human diploid cells at differing in vitro ages. Metabolic labeling of cellular proteins following a brief heat shock showed that the synthesis of heat shock proteins was significantly reduced in late-passage cells. Northern blot analyses revealed that the reduced expression of heat shock proteins in old cells correlated with a reduced accumulation of heat shock-specific transcripts. The attenuation of heat shock gene activity in senescent cells was not unique to thermal stress since exposure of cells to sodium arsenite (10-50 microM) elicited a similar response. The reduced expression of heat shock gene products correlated with an increased thermal lability in late-passage cells following acute hyperthermic (49 degrees C) exposure. The preinduction of heat shock genes protected cells against the lethal effects of acute hyperthermia and abolished the increased thermal lability observed in senescent cells. The reduced expression of the heat shock response demonstrates that old cells possess a diminished ability to withstand adverse environmental conditions and maintain homeostasis.
在不同体外传代年龄的人二倍体细胞中检测了三类主要热休克基因的表达。短暂热休克后对细胞蛋白质进行代谢标记显示，传代后期细胞中热休克蛋白的合成显著减少。Northern印迹分析表明，衰老细胞中热休克蛋白表达的降低与热休克特异性转录本积累的减少相关。衰老细胞中热休克基因活性的减弱并非热应激所特有，因为将细胞暴露于亚砷酸钠（10 - 50 microM）会引发类似反应。热休克基因产物表达的降低与传代后期细胞在急性高温（49℃）暴露后热稳定性增加相关。热休克基因的预诱导可保护细胞免受急性高温的致死效应，并消除衰老细胞中观察到的热稳定性增加。热休克反应表达的降低表明衰老细胞抵御不利环境条件并维持体内平衡的能力减弱。
