Instituto de Investigaciones Oftalmológicas "Ramón Castroviejo", Universidad Complutense de Madrid, Madrid, Spain.
PLoS One. 2013 Jun 7;8(6):e65446. doi: 10.1371/journal.pone.0065446. Print 2013.
Tumour-suppressor genes, such as the p53 gene, produce proteins that inhibit cell division under adverse conditions, as in the case of DNA damage, radiation, hypoxia, or oxidative stress (OS). The p53 gene can arrest proliferation and trigger death by apoptosis subsequent to several factors. In astrocytes, p53 promotes cell-cycle arrest and is involved in oxidative stress-mediated astrocyte cell death. Increasingly, astrocytic p53 is proving fundamental in orchestrating neurodegenerative disease pathogenesis. In terms of ocular disease, p53 may play a role in hypoxia due to ischaemia and may be involved in the retinal response to oxidative stress (OS). We studied the influence of the p53 gene in the structural and quantitative characteristics of astrocytes in the retina. Adult mice of the C57BL/6 strain (12 months old) were distributed into two groups: 1) mice with two extra copies of p53 ("super p53"; n = 6) and 2) wild-type p53 age-matched control, as the control group (WT; n = 6). Retinas from each group were immunohistochemically processed to locate the glial fibrillary acidic protein (GFAP). GFAP+ astrocytes were manually counted and the mean area occupied for one astrocyte was quantified. Retinal-astrocyte distribution followed established patterns; however, morphological changes were seen through the retinas in relation to p53 availability. The mean GFAP+ area occupied by one astrocyte in "super p53" eyes was significantly higher (p<0.05; Student's t-test) than in the WT. In addition, astroglial density was significantly higher in the "super p53" retinas than in the WT ones, both in the whole-retina (p<0,01 Student's t-test) and in the intermediate and peripheral concentric areas of the retina (p<0.05 Student's t-test). This fact might improve the resistance of the retinal cells against OS and its downstream signalling pathways.
肿瘤抑制基因,如 p53 基因,在不利条件下产生抑制细胞分裂的蛋白质,如在 DNA 损伤、辐射、缺氧或氧化应激(OS)的情况下。p53 基因可以通过多种因素导致细胞增殖停止并触发细胞凋亡。在星形胶质细胞中,p53 促进细胞周期停滞,并参与氧化应激介导的星形胶质细胞死亡。越来越多的证据表明,星形胶质细胞中的 p53 在协调神经退行性疾病发病机制方面起着至关重要的作用。就眼部疾病而言,p53 可能在缺血引起的缺氧中发挥作用,并可能参与氧化应激(OS)对视网膜的反应。我们研究了 p53 基因对视网膜星形胶质细胞结构和数量特征的影响。将 12 个月大的 C57BL/6 品系成年小鼠分为两组:1)携带两个额外 p53 基因的“超级 p53”(n = 6);2)野生型 p53 年龄匹配的对照组(WT;n = 6)。对每组的视网膜进行免疫组织化学处理以定位神经胶质纤维酸性蛋白(GFAP)。手动计数 GFAP+星形胶质细胞,并量化每个星形胶质细胞所占据的平均面积。视网膜星形胶质细胞的分布遵循既定模式;然而,由于 p53 的可用性,在视网膜中观察到形态变化。“超级 p53”眼中每个星形胶质细胞所占据的平均 GFAP+面积明显高于 WT(p<0.05;Student's t 检验)。此外,“超级 p53”视网膜中的星形胶质细胞密度明显高于 WT,无论是在整个视网膜(p<0.01,Student's t 检验)还是在视网膜的中间和周边同心区域(p<0.05,Student's t 检验)。这一事实可能提高了视网膜细胞对 OS 及其下游信号通路的抵抗力。