Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, Warsaw, Poland.
Laboratory of Cytometry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Aging (Albany NY). 2024 Aug 23;16(16):11796-11808. doi: 10.18632/aging.206080.
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.
细胞可能会对 DNA 损伤做出衰老反应，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节 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节中发挥作用。在这里，我们表明，用 2-溴棕榈酸（2-BP）处理衰老的人血管平滑肌细胞（VSMCs），2-BP 是一种蛋白质酰基转移酶抑制剂，与衰老表型的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。这些作用呈剂量依赖性，与总蛋白质棕榈酰化水平的显著降低有关。我们还表明，2-BP 的衰老修饰特性至少部分是通过下调与 DNA 损伤相关分子途径的元件来介导的，例如磷酸化的 p53。我们的数据表明，细胞衰老可能受到棕榈酰化的调节，这为这种翻译后修饰在与年龄相关的疾病中的作用提供了新的视角。
