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正常妊娠和子痫前期胎盘组织中 NEMO 蛋白的表达。

Placental Expression of NEMO Protein in Normal Pregnancy and Preeclampsia.

机构信息

Department of Medical Biotechnology, Medical University of Lodz, Zeligowskiego 7/9, Lodz, Poland.

Department of Obstetrics, Perinatology, and Gynecology, Polish Mother's Memorial Hospital-Research Institute in Lodz, Rzgowska 281/289, Lodz, Poland.

出版信息

Dis Markers. 2019 Jan 2;2019:8418379. doi: 10.1155/2019/8418379. eCollection 2019.

DOI:10.1155/2019/8418379
PMID:30723530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6339720/
Abstract

BACKGROUND

Preeclamptic pregnancies often present an intensified inflammatory state associated with the nuclear activity of NFB. NEMO is an essential regulator of nuclear factor kappa B (NFB) in cytoplasmic and nuclear cellular compartments. The aim of the present study is to examine the level and localization of the NEMO protein in preeclamptic and nonpreeclamptic placentas.

METHODS

The study includes 97 preeclamptic cases and 88 controls. NEMO distribution was analyzed immunohistochemically. Its localization in the nuclear and cytoplasmic fractions, as well as in total homogenates of placental samples, was studied by western blot and ELISA.

RESULTS

The western blot and ELISA results indicate a significant difference in NEMO concentration in the total and nuclear fractions between preeclamptic and control samples ( < 0.01 and < 0.001, respectively). In the cytoplasmic complement, similar levels of NEMO were found in preeclamptic and control placentas. In addition, immunohistochemical staining revealed that the NEMO protein is mainly localized in the syncytiotrophoblast layer, with controls demonstrating a stronger reaction with NEMO antibodies. This study also shows that the placental level of NEMO depends on the sex of the fetus.

CONCLUSIONS

The depletion of the NEMO protein in the cellular compartments of placental samples may activate one of the molecular pathways influencing the development of preeclampsia, especially in pregnancies with a female fetus. A reduction of the NEMO protein in the nuclear fraction of preeclamptic placentas may intensify the inflammatory state characteristic for preeclampsia and increase the level of apoptosis and necrosis within preeclamptic placentas.

摘要

背景

子痫前期妊娠常呈现出与核因子 kappa B(NFB)的核活性相关的强化炎症状态。NEMO 是细胞质和核细胞区室中核因子 kappa B(NFB)的必需调节剂。本研究旨在检测 NEMO 蛋白在子痫前期和非子痫前期胎盘组织中的水平和定位。

方法

本研究包括 97 例子痫前期病例和 88 例对照。通过免疫组织化学分析 NEMO 的分布。通过 Western blot 和 ELISA 研究其在胎盘样本的核和细胞质部分以及总匀浆中的定位。

结果

Western blot 和 ELISA 结果表明,子痫前期和对照组样本中 NEMO 浓度在总分数和核分数之间存在显著差异(分别为<0.01 和<0.001)。在细胞质补体中,子痫前期和对照组胎盘中的 NEMO 水平相似。此外,免疫组织化学染色显示 NEMO 蛋白主要定位于合体滋养层层,对照组与 NEMO 抗体的反应更强。本研究还表明,胎盘 NEMO 水平取决于胎儿的性别。

结论

胎盘样本细胞区室中 NEMO 蛋白的耗竭可能会激活影响子痫前期发展的分子途径之一,尤其是在怀有女性胎儿的妊娠中。子痫前期胎盘核分数中 NEMO 蛋白的减少可能会加剧子痫前期的炎症状态,并增加子痫前期胎盘内的细胞凋亡和坏死水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/4040099637da/DM2019-8418379.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/c505275adf2d/DM2019-8418379.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/061dfdedaa73/DM2019-8418379.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/6084daedae4b/DM2019-8418379.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/6168f6e7f3fb/DM2019-8418379.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/4040099637da/DM2019-8418379.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/c505275adf2d/DM2019-8418379.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/061dfdedaa73/DM2019-8418379.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/6084daedae4b/DM2019-8418379.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/6168f6e7f3fb/DM2019-8418379.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ef/6339720/4040099637da/DM2019-8418379.005.jpg

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本文引用的文献

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Pregnancy Hypertens. 2018 Jan;11:18-25. doi: 10.1016/j.preghy.2017.12.003. Epub 2017 Dec 21.
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The role of NFκB in the three stages of pregnancy - implantation, maintenance, and labour: a review article.NFκB 在妊娠三个阶段(着床、维持和分娩)中的作用:综述文章。
BJOG. 2018 Oct;125(11):1379-1387. doi: 10.1111/1471-0528.15172. Epub 2018 Mar 23.
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NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer.
药物靶向核因子 Kappa B 用于子痫前期的预防和治疗。
Int J Mol Sci. 2022 Mar 7;23(5):2881. doi: 10.3390/ijms23052881.
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Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia.子痫前期中核因子 кb 激活的经典、非经典和非典型途径。
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NEMO是雌激素和孕激素的转录靶点,与乳腺癌中的肿瘤抑制因子PML相关。
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Role for RIP1 in mediating necroptosis in experimental intracerebral hemorrhage model both in vivo and in vitro.RIP1在体内和体外实验性脑出血模型中介导坏死性凋亡中的作用。
Cell Death Dis. 2017 Mar 2;8(3):e2641. doi: 10.1038/cddis.2017.58.
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Augmented trophoblast cell death in preeclampsia can proceed via ceramide-mediated necroptosis.子痫前期中滋养层细胞死亡增加可通过神经酰胺介导的坏死性凋亡进行。
Cell Death Dis. 2017 Feb 2;8(2):e2590. doi: 10.1038/cddis.2016.483.
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