Vanhooren Valerie, Liu Xue-En, Desmyter Liesbeth, Fan Ye-Dong, Vanwalleghem Lieve, Van Molle Wim, Dewaele Sylviane, Praet Marleen, Contreras Roland, Libert Claude, Chen Cuiying
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Rejuvenation Res. 2008 Dec;11(6):1013-20. doi: 10.1089/rej.2008.0783.
Experiments in lower organisms, such as worms and flies, indicate that the molecular chaperone protein heat shock protein 70 (HSP70) is a longevity factor. In contrast, we demonstrate here that mice overexpressing HSP70 display growth retardation and early death. HSP70 transgenic mice displayed increased levels of serum corticosterone and weaker expression and activity of the glucocorticoid receptor in the liver. Serum insulin-like growth factor-1 (IGF-1) concentrations in the transgenic mice were 50% lower than in the control mice, leading to growth retardation. HSP70 transgenic mice showed decreased expression of Casp9, which encodes caspase-9, and increased expression of the anti-apoptotic Bcl-2 gene, indicating that apoptosis is suppressed. Consequently, most of the transgenic animals died before the age of 18 months from tumors in their lungs and lymph nodes. We suggest that the proinflammatory and antiapoptotic effects of HSP70 might be responsible for the growth retardation, tumor formation, and early death observed in the HSP70 transgenic mice.
在诸如蠕虫和果蝇等低等生物中进行的实验表明，分子伴侣蛋白热休克蛋白70（HSP70）是一种长寿因子。相比之下，我们在此证明，过度表达HSP70的小鼠表现出生长迟缓并过早死亡。HSP70转基因小鼠血清皮质酮水平升高，肝脏中糖皮质激素受体的表达和活性减弱。转基因小鼠血清胰岛素样生长因子-1（IGF-1）浓度比对照小鼠低50%，导致生长迟缓。HSP70转基因小鼠显示出编码半胱天冬酶-9的Casp9表达降低，以及抗凋亡Bcl-2基因的表达增加，表明细胞凋亡受到抑制。因此，大多数转基因动物在18个月龄之前死于肺部和淋巴结肿瘤。我们认为，HSP70的促炎和抗凋亡作用可能是导致HSP70转基因小鼠出现生长迟缓、肿瘤形成和过早死亡的原因。
