Adam Krzystyniak, Agata Gluchowska, Agata Pytyś, Magdalena Dudkowska, Tomasz Wójtowicz, Alicja Targonska, Dorota Janiszewska, Ewa Sikora, Grazyna Mosieniak
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引用次数: 0
Abstract
Cells may undergo senescence in response to DNA damage, which is associated with cell cycle arrest, altered gene expression and altered cell morphology. Protein palmitoylation is one of the mechanisms by which the DNA damage response is regulated. Therefore, we hypothesized that protein palmitoylation played a role in regulation of the senescent phenotype. Here, we showed that treatment of senescent human vascular smooth muscle cells (VSMCs) with 2-bromopalmitate (2-BP), an inhibitor of protein acyltransferases, is associated with changes in different aspects of the senescent phenotype, including the resumption of cell proliferation, a decrease in DNA damage markers and the downregulation of senescence-associated β-galactosidase activity. The effects were dose dependent and associated with significantly decreased total protein palmitoylation level. We also showed that the senescence-modifying properties of 2-BP were at least partially mediated by the downregulation of elements of DNA damage-related molecular pathways, such as phosphorylated p53. Our data suggest that cell senescence may be regulated by palmitoylation, which provides a new perspective on the role of this posttranslational modification in age-related diseases.
细胞可能会因 DNA 损伤而衰老,这与细胞周期停滞、基因表达改变和细胞形态改变有关。蛋白质棕榈酰化是调控 DNA 损伤反应的机制之一。因此,我们假设蛋白质棕榈酰化在衰老表型的调控中发挥作用。在这里,我们发现用蛋白酰基转移酶抑制剂 2-溴棕榈酸酯(2-BP)处理衰老的人血管平滑肌细胞(VSMCs)与衰老表型不同方面的变化有关,包括细胞增殖的恢复、DNA 损伤标志物的减少和衰老相关的 β-半乳糖苷酶活性的下调。这些影响与剂量有关,并与总蛋白棕榈酰化水平的显著降低有关。我们还发现,2-BP 的衰老修饰特性至少部分是通过下调 DNA 损伤相关分子通路的元素(如磷酸化的 p53)来介导的。我们的数据表明,细胞衰老可能受到棕榈酰化的调控,这为研究这种翻译后修饰在老年相关疾病中的作用提供了一个新的视角。