Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush

Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush
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视神经挤压后视网膜神经节细胞凋亡中 P53 诱导的死亡结构域蛋白上调的参与。

DOI：
10.2174/1566524019666190918160032
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发表时间：
2020
期刊：
Current Molecular Medicine
影响因子：
2.5
通讯作者：
Chen Qi
Chen Qi
中科院分区：
医学4区
文献类型：
--
作者：
Zhang Mingyuan;Chen Lifei;Xu Fan;Jiang Li;Yan Wenya;Kunwar Bibhav;Tang Fen;Yang Ke;Shen Chaolan;Huang Hui;Lv Jian;Qin Chen;Wu Xiaonian;Zeng Siming;Li Min;Zhong Shan;Chen Qi

文献摘要

相似文献

目的 视网膜神经节细胞凋亡是视神经病变的共同特征。p53-induced protein with a death domain（PIDD）是已知的遗传毒性应激诱导的细胞凋亡的调节剂，其被组成性切割成三个主要片段：PIDD-N、PIDD-C和PIDD-CC。因此，我们的目的是确定PIDD在视神经挤压（ONC）模型中RGCs凋亡的生理相关性。 方法 将所有动物随机分为4组：假手术对照组、con-siRNA组、ONC组和PIDD-siRNA组（ONC + PIDD-siRNA）。Western blot和免疫荧光法检测PIDD、caspase-2、Brn 3a和tBid在ONC模型中的表达。用荧光金（Fluoro-Gold，FG）法计算RGCs平均密度/mm 2。此外，我们使用TUNEL染色检测PIDD-siRNA对ONC诱导的RGCs凋亡的影响。 结果 全长PIDD水平较弱，在任何时间点均无显著差异。PIDD-CC和PIDD-C在ONC后3天在视网膜中显著上调。同时，PIDD在Brn 3a（RGCs的标志物）阳性细胞中的表达显著增加，表明PIDD似乎局限于RGCs。此外，抑制PIDD通过抑制caspase-2和tBid活化来防止RGCs凋亡。 结论 PIDD可能在ONC后RGCs凋亡中起重要作用，该过程可能与caspase-2和tBid有关。
PURPOSE Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. METHODS All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC + PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. RESULTS The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. CONCLUSIONS Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.