Department of Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida 33620, USA.
J Biol Chem. 2012 Aug 17;287(34):29045-53. doi: 10.1074/jbc.M112.353714. Epub 2012 Jul 9.
The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C. elegans strain with a sir2.1 deletion, we show that heat shock and caloric restriction cooperate to promote increased survivability and fitness in a sir2.1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1.
热休克反应（HSR）通过调节蛋白质稳态来维持细胞和机体的健康。最近的数据表明，哺乳动物的 HSR 受 SIRT1 调节，这表明该反应可能受到代谢控制。为了验证这一假说，我们已经确定了在秀丽隐杆线虫中热量限制对 HSR 激活的影响，并且发现它对 hsp70 基因表达的诱导具有协同作用。秀丽隐杆线虫中哺乳动物 SIRT1 的同源物是 Sir2.1。我们使用带有 sir2.1 缺失的突变秀丽隐杆线虫菌株表明，热休克和热量限制以 sir2.1 依赖的方式协同促进生存能力和适应性的提高。最后，我们表明热量限制可以提高热休克在聚谷氨酰胺毒性神经退行性疾病模型中维持运动的能力，并且这种作用依赖于 sir2.1。
