Evidence that the bifunctional redox factor/AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina
Evidence that the bifunctional redox factor/AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina
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DOI：
10.1038/sj.cdd.4400639
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发表时间：
2000-03-01
影响因子：
12.4
通讯作者：
Linden, R
中科院分区：
文献类型：
--
作者：
Chiarini, LB;Freitas, FG;Linden, R
视网膜细胞分化导致对由蛋白质合成抑制诱导的凋亡的抗性，表明抗凋亡蛋白的积累。氧化还原因子/AP核酸内切酶Ref-1（APE、APEX、HAP 1）影响DNA修复和各种转录因子的活性，并控制对遗传毒性损伤的敏感性。我们研究了Ref-1在发育大鼠视网膜和脑中的表达。Ref-1免疫反应性在分化中的视网膜细胞核内逐渐增加，而在发育中的海马结构中减少。在自然和实验诱导的细胞死亡过程中，Ref-1从凋亡细胞的细胞核中消失。Ref-1在轴突切断的神经节细胞中的降解先于凋亡的形态学特征。无论是毒胡萝卜素或冈田酸引发的细胞凋亡的敏感性是最高的光感受器，即：包含最少的Ref-1之间的分化的视网膜细胞。在这两种分化的细胞类型中，蛋白质合成的抑制阻止了Ref-1的丢失并拯救了神经元。这些数据表明Ref-1是与视网膜中的细胞分化相关的抗凋亡蛋白。
Retinal cell differentiation leads to resistance to apoptosis induced by inhibition of protein synthesis, suggesting the accumulation of anti-apoptotic proteins. The redox factor/AP endonuclease Ref-1 (APE, APEX, HAP1) affects both DNA repair and the activity of Various transcription factors, and controls sensitivity to genotoxic insults. We studied the expression of Ref-1 in the retina and brain of developing rats. Ref-1 immunoreactivity increased progressively within the nucleus of differentiating retinal cells, whereas it decreased in the developing hippocampal formation. During both natural and experimentally-induced cell death, Ref-1 disappeared from the nucleus of apoptotic cells. Degradation of Ref-1 in axotomized ganglion cells preceded the morphological characteristics of apoptosis. The sensitivity to apoptosis triggered by either thapsigargin or okadaic acid was the highest in photoreceptors, that: contain the least Ref-1 among differentiated retinal cells. In both these differentiated cell types, inhibition of protein synthesis prevented the loss of Ref-1 and rescued the neurons. The data suggest that Ref-1 is an anti-apoptotic protein associated with cell differentiation in the retina.