Department of Biochemistry, School of Medicine, Marmara University, 34854 Istanbul, Turkey.
Department of Molecular Biology and Genetics, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey.
Oxid Med Cell Longev. 2020 Feb 27;2020:9369524. doi: 10.1155/2020/9369524. eCollection 2020.
Aging has been characterized with the accumulation of oxidized proteins, as a consequence of progressive decline in proteostasis capacity. Among others, proteasomal system is an efficient protein turnover complex to avoid aggregation of oxidized proteins. Heat shock protein 70 (HSP70) is another critical player that is involved in some key processes including the correct folding of misfolded proteins and targeting aggregated proteins to the proteasome for rapid degradation. The aim of this study was to determine the role of proteasomal system and heat shock proteins to maintain proteome balance during replicative senescence in mild hyperthermia conditions. Our results demonstrated that HSP40/70 machinery is induced by mild hyperthermia conditions independent from senescence conditions. Since HSP70 is largely responsible for the rapidly inducible cell protection following hyperthermia, the activation of "heat shock response" resulted in the elevation of HSP40/70 expressions as well as the proteasome activity. Interestingly, when HSP70 expression was inhibited, increased proteasomal activation was shown to be responsive to mild hyperthermia. Since HSP70 is involved in various stress-related pathways such as oxidative and endoplasmic reticulum stress, depletion of HSP70 expression may induce proteasomal degradation to maintain proteome balance of the cell. Thus, our data suggests that in mild heat stress conditions, molecular chaperone HSP70 plays an important role to avoid protein oxidation and aggregation; however, activities of proteasomal system are induced when HSP70 expression is depleted.
衰老是由于蛋白质稳态能力的逐渐下降，导致氧化蛋白质的积累为特征的。其中，蛋白酶体系统是一种有效的蛋白质周转复合物，可避免氧化蛋白质的聚集。热休克蛋白 70（HSP70）是另一个关键参与者，它参与了一些关键过程，包括错误折叠蛋白质的正确折叠以及将聚集蛋白质靶向蛋白酶体进行快速降解。本研究的目的是确定蛋白酶体系统和热休克蛋白在轻度热应激条件下复制性衰老过程中维持蛋白质组平衡的作用。我们的研究结果表明，HSP40/70 机制在独立于衰老条件的轻度热应激条件下被诱导。由于 HSP70 主要负责在热应激后迅速诱导细胞保护，因此“热休克反应”的激活导致 HSP40/70 表达和蛋白酶体活性的升高。有趣的是，当抑制 HSP70 表达时，显示出对轻度热应激的蛋白酶体激活增加的反应性。由于 HSP70 参与各种与应激相关的途径，如氧化应激和内质网应激，因此 HSP70 表达的耗尽可能会诱导蛋白酶体降解以维持细胞的蛋白质组平衡。因此，我们的数据表明，在轻度热应激条件下，分子伴侣 HSP70 对于避免蛋白质氧化和聚集起着重要作用；然而，当 HSP70 表达耗尽时，蛋白酶体系统的活性会被诱导。
