过表达人p33^(ING1b)促进UV诱导的衰老细胞凋亡

Adenoviruses-mediated Over-Expression of p33^(ING1B) Promotes UV-Induced Apoptosis in Senescent Fibroblasts

p33ING1b是肿瘤抑制基因ING1的主要表达形式,已有的研究表明,p33ING1b参与了细胞的生长抑制、凋亡、染色质重塑、DNA损伤修复、肿瘤抑制等.但是,它在细胞衰老过程中的作用目前还不清楚.本研究分析了p33ING1b基因在细胞衰老过程中的表达情况.结果发现,无论在mRNA水平还是在蛋白水平,p33ING1b在衰老细胞中的表达均降低.通过构建和包装含p33ING1b基因的重组腺病毒,将p33ING1b导入衰老细胞中使其过表达,结果显示,p33ING1b的过表达明显促进UV诱导的衰老细胞凋亡,提示p33ING1b在衰老细胞中的表达下调与衰老细胞抗凋亡有关.

As one major isoform of ING1, p33^ING1b has been well documented in the past ten years since it was cloned. Previous studies show that p33^ING1b is involved in growth inhibition, apoptosis, chromatin remodeling, DNA repair and tumor suppression, but its biochemical function and involvement in cellular senescence is still not fully characterized. In this study, we first examined p33^ING1b expression level in senescent and young cells, the results showed that the expression levels of p33^ING1b in senescent cells are down-regulated contrary to young cells at whether transcriptional level or translational level. Next, we constructed adenoviruses encoding for p33^ING1b to investigate whether ectopic over-expression of p33^ING1b has an effect on senescent cellular apoptosis as senescent cells are contradictory to apoptotic inducer, the result showed adenoviruses-mediated over-expression of p33^ING1b in senescent cells can enhance cellular apoptosis which was examined by Hoechst 33258 staining. These results suggested that decreased expression of p33^ING1b may be related to the contradiction of senescent cells to aoootosis.