Imaging and quantification of amyloid fibrillation in the cell nucleus.

Imaging and quantification of amyloid fibrillation in the cell nucleus.
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细胞核中淀粉样纤维颤动的成像和定量

DOI:
10.1007/978-1-4939-1680-1_15
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发表时间:
2015
影响因子:
--
通讯作者:
von Mikecz A
von Mikecz A
中科院分区:
--
文献类型:
--
作者:
Arnhold F;Scharf A;von Mikecz A

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外源性物质以及细胞老化等内在过程,导致了一个不断挑战核组织和功能的环境。虽然越来越清楚的是,蛋白酶体依赖的蛋白水解是一个主要的球员,核蛋白稳态的拓扑结构和分子机制仍然在很大程度上未知。我们以前已经表明,(1)蛋白酶体依赖的蛋白质降解是在整个核质的焦点微环境中组织的,(2)重金属以及纳米颗粒诱导具有淀粉样蛋白特征的核蛋白纤维化。在这里,我们描述了在不同系统(例如哺乳动物细胞培养物和土壤线虫秀丽隐杆线虫)中在全球和局部水平上表征核内淀粉样蛋白景观的方法。应用离散数学的成像数据作为一种工具,开发细胞内蛋白质纤维化的模式识别。由于可溶性蛋白质逐步纤维化为不溶性淀粉样蛋白聚集体是神经退行性蛋白质错误折叠疾病(包括阿尔茨海默病、CAG重复疾病和朊病毒脑病)的标志,因此对细胞内淀粉样蛋白的研究同样有助于更好地理解所涉及的病理机制。我们认为聚集体分析是一种重要的实验方法,以确定核淀粉样蛋白是否在各种疾病过程中具有毒性或保护作用。
Xenobiotics, as well as intrinsic processes such as cellular aging, contribute to an environment that constantly challenges nuclear organization and function. While it becomes increasingly clear that proteasome-dependent proteolysis is a major player, the topology and molecular mechanisms of nuclear protein homeostasis remain largely unknown. We have shown previously that (1) proteasome-dependent protein degradation is organized in focal microenvironments throughout the nucleoplasm and (2) heavy metals as well as nanoparticles induce nuclear protein fibrillation with amyloid characteristics. Here, we describe methods to characterize the landscape of intranuclear amyloid on the global and local level in different systems such as cultures of mammalian cells and the soil nematodeCaenorhabditis elegans. Application of discrete mathematics to imaging data is introduced as a tool to develop pattern recognition of intracellular protein fibrillation. Since stepwise fibrillation of otherwise soluble proteins to insoluble amyloid-like protein aggregates is a hallmark of neurodegenerative protein-misfolding disorders including Alzheimer’s disease, CAG repeat diseases, and the prion encephalopathies, investigation of intracellular amyloid may likewise aid to a better understanding of the pathomechanisms involved. We consider aggregate profiling as an important experimental approach to determine if nuclear amyloid has toxic or protective roles in various disease processes.
用于检测类淀粉样聚谷氨酰胺的蛋白质聚集体的膜过滤测定。
DOI: 10.1016/s0076-6879(99)09026-6
发表时间: 1999
影响因子: --
作者:
Erich E. Wanker;Eberhard Scherzinger;Volker Heiser;A. Sittler;Holger Eickhoff;H. Lehrach
通讯作者: H. Lehrach
表达多聚谷氨酰胺扩展蛋白的神经元的纵向成像和分析。
DOI: 10.1007/978-1-62703-438-8_1
发表时间: 2013
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者:
Tsvetkov,AndreyS;Ando,DMichael;Finkbeiner,Steven
通讯作者: Finkbeiner,Steven
DOI: 10.1007/978-1-62703-640-5_2
发表时间: 2013
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者:
Kovalevich, Jane;Langford, Dianne
通讯作者: Langford, Dianne
生物纳米成像:蛋白质错误折叠和聚集
DOI: --
发表时间: 2013
期刊:
影响因子: --
作者:
V. Uversky;Y. Lyubchenko
通讯作者: Y. Lyubchenko
细胞培养物或模型生物秀丽隐杆线虫中转录和蛋白酶体蛋白水解的等时可视化。
DOI: 10.1007/978-1-62703-526-2_19
发表时间: 2013
影响因子: --
作者:
A. von Mikecz;A. Scharf
通讯作者: A. Scharf