In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated from Porphyromonas gingivalis.
In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated from Porphyromonas gingivalis.
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DOI：
10.3390/ijms241713351
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发表时间：
2023-08-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
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本研究的目的是阐明暴露于牙龈卟啉单胞菌（Pg）口腔细菌产生的外膜囊泡（OMV）后，人神经母细胞瘤细胞的细胞变性化学，通过监测其代谢组学的演变，使用原位拉曼光谱。Pg-OMV是阿尔茨海默病（AD）发病机制中的关键因素，因为它们充当用于递送促进神经元损伤的毒素的有效载体。然而，Pg-OMV在分子水平上对细胞代谢物的直接影响的化学机制仍然明显不清楚。采用神经母细胞瘤SH-SY 5 Y细胞（SK-N-SH细胞系的亚系）的广泛使用的体外模型在Pg-OMV污染之前和之后6小时原位进行光谱分析。同时，还对分离的Pg-OMV进行了拉曼表征，其中包括磷酸化二氢神经酰胺（PDHC）脂质和脂多糖（LPS），后者又被一类高致病性半胱氨酸蛋白酶污染，半胱氨酸蛋白酶是神经元细胞降解的关键因素。拉曼特征定位脂多糖指纹的囊泡结构，并揭示了迄今为止尚未证实的方面的蛋白质降解背后的Pg-OMV污染的SH-SY 5 Y细胞诱导的化学。观察到的细胞拉曼谱的改变，然后讨论的关键因素，包括淀粉样蛋白β（Aβ）斑块和过度磷酸化的Tau神经元缠结的形成，和胆固醇聚集体的形成，加剧AD病理。
The aim of this study was to elucidate the chemistry of cellular degeneration in human neuroblastoma cells upon exposure to outer-membrane vesicles (OMVs) produced by Porphyromonas gingivalis (Pg) oral bacteria by monitoring their metabolomic evolution using in situ Raman spectroscopy. Pg-OMVs are a key factor in Alzheimer’s disease (AD) pathogenesis, as they act as efficient vectors for the delivery of toxins promoting neuronal damage. However, the chemical mechanisms underlying the direct impact of Pg-OMVs on cell metabolites at the molecular scale still remain conspicuously unclear. A widely used in vitro model employing neuroblastoma SH-SY5Y cells (a sub-line of the SK-N-SH cell line) was spectroscopically analyzed in situ before and 6 h after Pg-OMV contamination. Concurrently, Raman characterizations were also performed on isolated Pg-OMVs, which included phosphorylated dihydroceramide (PDHC) lipids and lipopolysaccharide (LPS), the latter in turn being contaminated with a highly pathogenic class of cysteine proteases, a key factor in neuronal cell degradation. Raman characterizations located lipopolysaccharide fingerprints in the vesicle structure and unveiled so far unproved aspects of the chemistry behind protein degradation induced by Pg-OMV contamination of SH-SY5Y cells. The observed alterations of cells’ Raman profiles were then discussed in view of key factors including the formation of amyloid β (Aβ) plaques and hyperphosphorylated Tau neurofibrillary tangles, and the formation of cholesterol agglomerates that exacerbate AD pathologies.
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影响因子：
--
作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
4.8
作者：
Avila J;Jiménez JS;Sayas CL;Bolós M;Zabala JC;Rivas G;Hernández F
通讯作者：
Hernández F
DOI：
10.1073/pnas.96.7.3590
发表时间：
1999-03-30
影响因子：
11.1
作者：
Chiti, F;Webster, P;Dobson, CM
通讯作者：
Dobson, CM
影响因子：
21.3
作者：
Cohen, P
通讯作者：
Cohen, P
影响因子：
5.5
作者：
Breitzig, Mason;Bhimineni, Charishma;Kolliputi, Narasaiah
通讯作者：
Kolliputi, Narasaiah