Ladiges W, Morton J, Blakely C, Gale M
The Nathan Shock Center for Excellence in the Biology of Aging, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Mech Ageing Dev. 2000 Mar 13;114(2):123-32. doi: 10.1016/s0047-6374(00)00097-x.
A decline in the rate of protein synthesis is a common biochemical change observed with aging in a wide variety of cells and organisms. The double stranded RNA-dependent protein kinase PKR has been shown to phosphorylate eukaryotic initiation factor 2 alpha (eIF-2alpha), a well-characterized factor for down-regulating protein synthesis, in response to environmental stress conditions. Therefore, we were interested in evaluating the role of PKR in the aging process. Tissues from 2- and 20-month-old B6D2F1 male mice were evaluated by Western blot analysis. PKR was detected in all tissues of aging mice confirming its ubiquitous nature. Tissues examined from young mice showed little evidence of PKR expression, suggesting an age-associated up-regulation. P58(IPK), a cellular inhibitor of PKR, was expressed in tissues from both age groups but to a greater extent in tissues of aging mice suggesting an up-regulation to control PKR activity. Hyperphosphorylated eIF-2alpha was increased in selected tissues from older mice compared with tissues from younger mice indicating a possible correlation between PKR expression and kinase function. The data suggest that translational activity is slowing down in a tissue specific manner during the aging process in mice, possibly as the result of increased levels of PKR, and could be a factor in the reduction of the rate of protein synthesis during senescence seen in specific tissues of many organisms.
蛋白质合成速率下降是在多种细胞和生物体衰老过程中常见的生化变化。双链RNA依赖性蛋白激酶PKR已被证明在环境应激条件下可磷酸化真核起始因子2α（eIF-2α），这是一种下调蛋白质合成的特征明确的因子。因此，我们有兴趣评估PKR在衰老过程中的作用。通过蛋白质印迹分析评估2月龄和20月龄B6D2F1雄性小鼠的组织。在衰老小鼠的所有组织中均检测到PKR，证实了其普遍存在的性质。从小鼠检测的组织中几乎没有PKR表达的证据，表明与年龄相关的上调。P58（IPK）是PKR的一种细胞抑制剂，在两个年龄组的组织中均有表达，但在衰老小鼠的组织中表达程度更高，表明其上调以控制PKR活性。与年轻小鼠的组织相比，老年小鼠某些组织中过度磷酸化的eIF-2α增加，表明PKR表达与激酶功能之间可能存在相关性。数据表明，在小鼠衰老过程中，翻译活性以组织特异性方式减慢可能是PKR水平升高的结果，并且可能是许多生物体特定组织衰老过程中蛋白质合成速率降低的一个因素。
