Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration.
Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration.
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C/EBP同源蛋白的消融不能保护T17M Rho小鼠免受视网膜变性的影响。
DOI：
10.1371/journal.pone.0063205
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gorbatyuk M
中科院分区：
文献类型：
--
作者：
Nashine S;Bhootada Y;Lewin AS;Gorbatyuk M
尽管提出了CHOP蛋白的消融和延迟ER应激介导的疾病（包括糖尿病、阿尔茨海默病和心脏肥大）的发作之间的联系，但CHOP蛋白在与常染色体显性视网膜色素变性（ADRP）相关的感光细胞死亡中的作用尚未研究。T17 M RHO转基因小鼠携带突变的人视紫红质转基因，其在视网膜中的表达导致蛋白质错误折叠、UPR激活和进行性视网膜变性。本研究旨在探讨CHOP蛋白在T17 M RHO视网膜中的作用。在研究中使用野生型、CHOP-/-、T17 M RHO和T17 M RHO CHOP-/-小鼠。使用视网膜电图（ERG）、光谱域光学相干断层扫描（SD-OCT）、定量实时PCR（qRT-PCR）和蛋白质印迹分析评价CHOP消融术的影响。暗适应ERG分析表明，与T17 M RHO小鼠相比，T17 M RHO CHOP−/−小鼠的a波振幅降低了70%。T17 M RHO CHOP−/−光感受器的功能丧失与外核层厚度下降22-24%有关。这些小鼠的转录因子Crx和Nrl的表达显著降低，小鼠Rho和人Rho的表达也显著降低。这种减少与UPR标记物p-eIf 2 α蛋白升高8倍和sXbp 1蛋白下调30%相关。此外，组蛋白去乙酰化酶1（Hdac 1）蛋白在T17 M RHO CHOP−/−视网膜中升高了2倍。CHOP的消融导致光受体特异性转录因子以及内源性和外源性RHO mRNA的表达减少。因此，尽管其在促进细胞凋亡中的作用，CHOP保护携带ADRP突变的视杆细胞感光器。
Despite the proposed link between ablation of the CHOP protein and delay of the onset of ER stress-mediated disorders including diabetes, Alzheimer Disease, and cardiac hypertrophy, the role of CHOP protein in photoreceptor cell death associated with Autosomal Dominant Retinitis Pigmentosa (ADRP) has not been investigated. T17M RHO transgenic mice carry a mutated human rhodopsin transgene, the expression of which in retina leads to protein misfolding, activation of UPR and progressive retinal degeneration. The purpose of this study is to investigate the role of CHOP protein in T17M RHO retina. Wild-type, CHOP−/−, T17M RHO and T17M RHO CHOP−/−mice were used in the study. Evaluation of the impact of CHOP ablation was performed using electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), quantitative Real-Time PCR (qRT-PCR) and western blot analysis. Dark-adapted ERG analysis demonstrated that by 1 month, the T17M RHO CHOP−/− mice had a 70% reduction of the a-wave amplitude compared to the T17M RHO mice. The loss of function in T17M RHO CHOP−/− photoreceptors was associated with a 22–24% decline in the thickness of the outer nuclear layer. These mice had significant reduction in the expression of transcription factors, Crx and Nrl, and also in mouse Rho, and human RHO. The reduction was associated with an 8-fold elevation of the UPR marker, p-eIf2α protein and 30% down-regulation of sXbp1 protein. In addition, the histone deacetylase 1 (Hdac1) protein was 2-fold elevated in the T17M RHO CHOP−/− retina. The ablation of CHOP led to a reduction in the expression of photoreceptor-specific transcriptional factors, and both endogenous and exogenous RHO mRNA. Thus, despite its role in promoting apoptosis, CHOP protects rod photoreceptors carrying an ADRP mutation.
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影响因子：
30.8
作者：
Mears, AJ;Kondo, M;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
21.3
作者：
Feng, B;Yao, PM;Tabas, I
通讯作者：
Tabas, I
DOI：
10.1042/bj20101293
发表时间：
2011-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Wang FM;Chen YJ;Ouyang HJ
通讯作者：
Ouyang HJ
白藜芦醇触发促凋亡的内质网应激反应，并抑制人类多发性骨髓瘤细胞中的促生物性XBP1信号传导。
影响因子：
2.6
作者：
Wang, Feng-Ming;Galson, Deborah L.;Roodman, G. David;Ouyang, Hongjiao
通讯作者：
Ouyang, Hongjiao
DOI：
10.1083/jcb.201110131
发表时间：
2012-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wang S;Kaufman RJ
通讯作者：
Kaufman RJ