Salmon Adam B, Ljungman Mats, Miller Richard A
Cellular and Molecular Biology Graduate Program, University of Michigan Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
J Gerontol A Biol Sci Med Sci. 2008 Mar;63(3):219-31. doi: 10.1093/gerona/63.3.219.
Fibroblasts isolated from long-lived hypopituitary dwarf mice are resistant to many cell stresses, including ultraviolet (UV) light and methyl methane sulfonate (MMS), which induce cell death by producing DNA damage. Here we report that cells from Snell dwarf mice recover more rapidly than controls from the inhibition of RNA synthesis induced by UV damage. Recovery of messenger RNA (mRNA) synthesis in particular is more rapid in dwarf cells, suggesting enhanced repair of the actively transcribing genes in dwarf-derived cells. At early time points, there was no difference in the repair of cyclobutane pyrimidine dimers (CPD) or 6-4 photoproducts (6-4PP) in the whole genome, nor was there any significant difference in the repair of UV lesions in specific genes. However, at later time points we found that more lesions had been removed from the genome of dwarf-derived cells. We have also found that cells from dwarf mice express higher levels of the nucleotide excision repair proteins XPC and CSA, suggesting a causal link to enhanced DNA repair. Overall, these data suggest a mechanism for the UV resistance of Snell dwarf-derived fibroblasts that could contribute to the delay of aging and neoplasia in these mice.
从长寿的垂体功能减退侏儒小鼠分离出的成纤维细胞对多种细胞应激具有抗性，包括紫外线（UV）和甲基磺酸甲酯（MMS），它们通过产生DNA损伤诱导细胞死亡。在此我们报告，来自斯内尔侏儒小鼠的细胞比对照细胞从紫外线损伤诱导的RNA合成抑制中恢复得更快。特别是信使RNA（mRNA）合成在侏儒细胞中恢复得更快，这表明侏儒来源细胞中活跃转录基因的修复增强。在早期时间点，全基因组中环丁烷嘧啶二聚体（CPD）或6-4光产物（6-4PP）的修复没有差异，特定基因中紫外线损伤的修复也没有任何显著差异。然而，在后期时间点，我们发现侏儒来源细胞的基因组中更多的损伤已被去除。我们还发现侏儒小鼠的细胞表达更高水平的核苷酸切除修复蛋白XPC和CSA，这表明与增强的DNA修复存在因果关系。总体而言，这些数据提示了斯内尔侏儒来源的成纤维细胞抗紫外线的一种机制，这可能有助于延缓这些小鼠的衰老和肿瘤形成。
